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Saturday, 2 June 2012
How women can decrease the risk of diabetes
Women who choose plain water over sweet fizzy drinks or fruit juice have a lower risk of developing diabetes, a new study has revealed. According to researchers at the Harvard School of Public Health, replacing sweet drinks with water could help stave off the metabolic disorder, but
adding water to the sugary beverages a person consumes throughout the day won't make a difference.
WomanThe results are based on the drinking habits of 83,000 women followed for more than a decade.
Lead researcher Frank Hu said it is well established that sugary beverages are bad for diabetes risk.
People have recommended drinking plain water instead of sugar-sweetened beverages, he said, "and the question is whether this kind of substitution has any impact on diabetes".
Hu and his team collected data from the massive Nurses Health Study, which tracked the health and lifestyle of tens of thousands of women across the U.S.
The study included 82,902 women who answered questions about their diet and health over a 12-year span.
Over time, about 2,700 of them developed diabetes.
The amount of water women drank did not seem to influence their diabetes risk - those who drank more than six cups a day had the same risk as women who drank less than one cup a day.
However, sugar-sweetened drinks and fruit juice were tied to a higher risk of diabetes - about 10 percent higher for each cup consumed each day.
The research team estimated that if women replaced one cup of fizzy drink or fruit juice with one cup of plain water, their diabetes risk would fall by 7 or 8 percent.
While it is not a huge reduction in the risk, "because diabetes is so prevalent in our society, even 7 or 8 percent reduction in diabetes risk is quite substantial in terms of the population," Hu said.
About 10 per cent of women, or 12.6million, have diabetes in the U.S.
A 7 percent reduction would mean that instead of ten out of every 100 women having diabetes, the number would be closer to nine out of every 100.
The study also found that unsweetened coffee or tea might be a good alternative to sugary beverages.
The researchers estimated that replacing one cup of a carbonated drink or fruit juice with one cup of coffee or tea could reduce the risk of developing diabetes by 12 to 17 percent.
Hu said the study is important in pointing out that fruit juice is not an optimal substitute for soda or other sugar-sweetened drinks.
"The reality is those juices contain the same amount of calories and sugar as soft drinks," the Daily Mail quoted him as saying.
The bottom line, he said, is that plain water is one of the best calorie-free choices for drinks, and "if the water is too plain, you can add a squeeze of lemon or lime".
The study has been published in the American Journal of Clinical Nutrition.
Posted by Admin at 17:47
Labels: health
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"Bill, are you there? It's me, Zygi."
It likely doesn't behoove Viking head coach Brad Childress that his name isn't something like, "Brad Hotcocoadress," or "Brad Fuzzystuffedanimaldress." Alas, "Chilly's" name is what it is and his moniker unfortunately echoes fan reception to his coaching skills as the Purple stand at 3-4, and Childress sports a career coaching mark of 17-22.
The Bye week has become the Bile week. Childress was brought here from Philadelphia with a reputation for offense, and, at least statistically, he hasn't wholly disappointed in that effect. While the Vikings ranked 26th in league points and 23rd in total yardage in Childress' nascent year of '06, he brought them to numerical respectability in said categories last year, scoring the 15th most points in the NFL and accruing the 13th best yardage tally. Through the Vikings first seven games of '08, they presently rank a digestible 18th in points (at 22.0 per) and 6th in yardage.
Of the Vikings first seven opponents this year, 5 are .500 or better, and those teams collectively posses a .540 win percentage. Of our remaining 9 opponents, 7 are .500 or better and the teams own a mirrored winning clip of .540.
Owner Zygi Wilf is both smart enough and classy enough to realize that there is rarely any salvation found in quitting on a coach mid-season. Yet, if Childress can't formulate an actual identity for this talented group and put together an ardent playoff push, he'll be gone.
And the top replacement would be former Pittsburgh Steeler head coach Bill Cowher. Out of coaching and working as an NFL analyst for CBS the last two years, Cowher is just 51 years old, and it would be a shock should he not return to coaching in the next season or two. His résumé includes the following:
-14th all-time in NFL coaching wins with 161 -11th best win percentage (.619) among coaches with 100 or more wins -.500 or better record in 12 of his 15 season with Pittsburgh (1992-2006), including 9 seasons with double-digit wins and 10 playoff appearances -2 Super Bowl appearances; won Super Bowl in 2005
Nice. Cowher last worked with a contract just over $4 million, although he'd likely command a raise to be paid among the league's six highest-paid coaches. That wouldn't be a problem for the Wilf family, which has evidenced their willingness to open the check book to acquire quality (or simply acceptable, at times) personnel.
Cowher would supply the Purple with what they seem most desperate for: A personality. And a hard-ass one at that. This campaign is far from over, and even at 3-4, the Vikings remain just a game removed from first in the NFC North. But on a week-to-week, we just never know what we're going to see -- and that's a confusing facet of fandom that usurps any statistic. Here's how Chilly stacks up with the respective win percentages of head coaches from Minnesota's other Big 4 pro teams:
Gardy: .549 win percentage
Jacques: .470 percentage points earned, divided by maximum points
Childress: .436 win percentage
Wittman: .274 win percentage

subset: commoncrawl


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We have another wonderfully creative layout class starting at PageMaps U June 30th. To our alumni who participated in the first class, this one is even bigger and better! And if you were not part of Class 1, you definitely don't want to miss this one!
This four-week course is fully loaded with concise, step-by-step pdf instructions, full color photos and close-ups, 12x12 single and double layouts (and three bonus 8.5x11 vertical layouts!), full measurements, how-to photos, electronic cutting files, pdf slideshows and so much more!
Registration closes Sunday June 29th, so register today!
See you in class!


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Over the years, Willclaim Solicitors have helped many individuals to successfully contest a will and claim what is rightfully theirs working on a No Win – No Fee basis.
Listed below are a few of the comments we have received from these individuals:-
I used this firm for a disputed probate claim and the professionalism shown was excellent. Phone calls were responded to, letters and information sent out and I felt the firm were 'really on my side'. My case was explained to me and communication was clear and responsive and indeed a resolution was obtained quickly. When you are grieving the loss of someone this is important and I truly felt that my feelings were listened to and that I wasn't just part of a legal machine. Thoroughly recommended. Ms L – (January 2019)
I am so glad it is all over, and so happy I had you on my side. I can confirm that the money is in, and thank you. – Ms D (August 2018)
I can't thank you enough for providing someone of Ms Amy Berry's calibre, as you rightly say "horses for courses", a brilliant woman…..Last but not least my sincere thanks to you for all your support through this ghastly business – Mrs H ( May 2017).
Thank you so much for all your hard work over the last number of months, I really do appreciate what you have done for me. It's kind of strange the feeling that I have now as since January of last year when everything fell apart I have had a massive emotional weight on my shoulders the worry the feeling that at a moments notice my Aunt could have me on the street. All things that led to a version of myself that was a emotional shadow of what I once was. With what you have done you have helped my future and more importantly than that you have lifted the fears of what my Aunt could do of me. And brought fairness to the situation. – Mr H (May 2017)
I would like to say a VERY BIG THANK YOU for all your help that you gave to successfully bring to an end a very bitter family dispute. – Mr P (April 2017)
I just wanted to convey my thanks for the past 5 months and all of your hard work, help and stress relief you have offered the family. It is more than appreciated by all of us including the extended family you haven't met of course. The stress relief of today in providing a complete and final outcome is immeasurable – Mr W (February 2016)
It was lovely to meet you again. If anyone else dies and I need to contest a will again I will certainly be getting in touch! My future has been in your hands for a long time – and thankfully you did a splendid job and now I can start to get on with my life – Miss M (January 2016)
Thank you so very much for sorting this out…..you have truly made such a difference to our lives – Debi T
I just wanted to say a big thank you for dealing with my case so promptly and efficiently as humanly possible – Julie F
Thanks again for everything that you have done for us we would not have got this far without you – Carole S
It's good to receive a bit of good news and thank you for everything – Garry O


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Article 8- update
Trainer: Mavelyn Vidal
Level: All levels
CPD: 2.5 hrs
Start: 14th March, 2019 at 5:00pm
End: 14th March, 2019 at 7:30pm
The course will look at the relationship between Article 8 and the Immigration Rules since 9 July 2012 and future developments. We will also look at the recent successful case of PD (Sri Lanka) and how it has clarified the seven-year rule for children; the effect of MM in the Supreme Court on the income threshold and on Home Office policy; and the effect of Kiarie and Byndloss on appeals in Article 8 cases.
· PD (Sri Lanka) and the seven year rule for children
-Establishment of a private and family life
-Engagement of Article 8 ECHR
-The concept of interference with Article 8 rights being in accordance with the law
-The concept of interference with Article 8 rights being necessary in a democratic society
· SF and Others and the approach to be taken by the Tribunal to Home Office policies
· MM, proportionality of the income threshold, and the Home Office policy on children
· Kiarie and Byndloss and in-country rights of appeal in Article 8 cases
Future developments
· Policy developments following MM
· The new Immigration Bill
Objectives - at the end of the course delegates will have an up to date knowledge of recent case law and its implications and will be in a better position to assist their clients.
To book this course, please visit https://www.jcwi.org.uk/Event/article-8-update
- EIN Regions:
- London
- Type of event:
- Legal training


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Welcome to the OSI VISION online benefits enrollment website. To access the site for the first time, please review your new hire notification for details on how to log on. If you cannot remember your password, please contact your Benefits Specialist at G&A Partners to have it reset.
Important Information
Questions about benefit plans and enrollment should be directed to G&A Partners by calling 1-866-497-4222


text:
A quick special offer code for one week only.
I have a code for Facebook groupies. This because the wee sheep are having a price rise. Please add sheep2017 when ordering a sheep and the old price will apply. In general all my costs have risen and I have tryied to maintain the sheep price for a long time, anyway same old story for us all. The new price is £125 but for one week only £105 with the code.


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The Polk Vision Literacy Team is leading a county-wide effort to develop a Literacy Resource Directory for PK-12 students and their families. The directory will be used by school counselors, administrators, teachers, and others in the Polk County Public School District. The Team's goal is to include as many literacy resources as possible that are available for students.
How You Can Help
The Literacy Team is reaching out to the community to engage partners who can offer literacy support and services.
To learn more about the Literacy Directory and Polk Vision click here.
Register here.
Your comment will be posted after it is approved.
Leave a Reply.


text: Training/Jens: Most dynamic moves start with a small rubber band swing. The elastic swing helps you to increase the dynamic force. In order to swing the centre of gravity, you can swing your body, the head and bend the legs or arms. Start by moving towards the next hold than swing backwards, stretching out the cord and than use that extra momentum for the next hold. The easiest way to train this technique is to make exaggerated swings, climb like a monkey :-)


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Cheltenham 01242 234499
Thornbury 01454 418003
We offer a FREE collection & Delivery Service to the following areas. Please contact us if your area is not shown.
Berkeley, Cam & Dursley, Slimbridge, Wotton under Edge, Charfield, Stonehouse.
(some of these areas are covered by our agencies)
Cheltenham, Hatherley, Charlton Kings, Leckhampton, Prestbury, Pittville.
Thonbury, Alveston, Almondsbury,
Excellent customer service 5*****
Hard Pressed For TimeI recently had some wedding attire dry cleaned in this shop. I must say the staff were very very friendly, extremely helpful in advising on the best way to clean the wedding dress and bridesmaid outfits. I was a little worried about the outcome as the garments were needed for a forthcoming wedding but I no need to have had any worries at all. When I collected all of the items they were in absolutely like new condition! They had even carried out a few minor repairs at no extra cost! I would highly recommend this shop. Full marks to Hard Pressed for Time and their staff.
I always used the other dry cleaners in Thornbury but called into this one a few weeks ago as I managed to find a parking space in the High street. The staff were really friendly, I collected my suit later that day! and they had even secured a loose button at no extra charge! Excellent service and, from the looks of it a very successful one as they appeared very busy!
Excellent cleaning done on time & pressed well. Lovely..
Excellent cleaning done on time & pressed well. Lovely friendly staff
I have used this Dry cleaners and the service I got was very good.
We Promise Satisfaction
Clean & Fresh


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October 1, 2012 Perrysburg, Ohio
The Northwest Ohio Conservative Coalition is excited to announce the first of several debate focused events in a countdown to the 2012 Presidential election. On Wednesday, October 3, the NWOCC will host a 'Debate Watching Party' from 8:00 p.m. to 10:00 p.m. The event will be held at Design Entertainment, 7015 Lighthouse Way, Ste. 300 south of Levis Commons in Perrysburg.
"We really want people to be engaged in this election", said Assistant Treasurer, Linda Bowyer. "We're excited to host an event where people can watch the first debate between Romney and Obama, and also get on the schedule of volunteers for both before and on election day".
Individuals who are interested in attending should RSVP via the link below:
For more information about this event, please email nwohioconservativecoalition@
To learn more about the Northwest Ohio Conservative Coalition, please visit www.nwohiocc.com, follow us on Twitter @NWOPatriots or find us on Facebook at www.facebook.com/


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Abby Lee Miller breaks silence following prison sentence
She was sentenced to one year and one day in prison for bankruptcy fraud and bringing $120,000 worth of Australian currency into the US without reporting it, but before she does her time, Dance Moms star Abbey Lee Miller has spoken on Good Morning America.
The reality TV star told the show she "wasn't ever trying to hurt anyone" in response to claims she was attempting to hide cash from her creditors, Fox News reports.
She then revealed how she plans to spend her time in prison.
"I'm just going to pretend that I am shooting a movie, and we're on set, and I am there for 10 months, and that's the way it's gonna be," she said.
"A year and a day; it sounds like a movie title."
Miller also revealed plans to learn Spanish while in prison and hone her businesswoman skills.
The clincher: "I am already working on a new book."
This article originally appeared on MarieClaire.com.
You may also like...


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Flat Francis Project
To keep the momentum going from Pope Francis' wonderful trip to the United States, we have initiated the "Flat Francis Project". Each week a different student (grades Pre-K through 5) takes home our Flat Francis folder. In the folder the family will find Flat Francis, a battery candle, a listing of the Pope's intentions for the month and instructions asking the family to pray with Francis each day for a week, then take a photo or a video of your family with Flat Francis doing something you like to do together and email it to email@example.com We are also including a prayer card with information regarding Pope Francis to keep in their home to continue their prayers after Flat Francis has left. We will post the photos here when they arrive. Let's make this a fun project!!


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Traffic police to no longer charge cash fines
Traffic regulation violators will have to pay traffic fines through their bank accounts starting December 1, as the traffic police will be equipped with devices that recognize drivers' fingerprints, ID cards, or driving licenses, and will instantly print traffic tickets.
The device will be distributed on November 29, to all 400 traffic regulation officials currently servicing Ulaanbaatar.
If traffic violators do not pay their fine by its due date, the fine will increase.
The devices were brought in though the state budget 2013, specifically, the purchase and other expenses were allocated from the Prime Minister's budget.
Short URL: http://ubpost.mongolnews.mn/?p=6749


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Carpet Cleaning Special Offers for May
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- £13.99*Hallway Carpet- (saving over 50%)
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- £120*2 Bedroom House- ALL carpets cleaned!
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*Prices are dependent on room size.
The minimum spend to call us out is £50. All prices exclude VAT.
Welcome to Aquadri Carpet Cleaning
Professional & quality led carpet cleaning specialists
Aquadri are one of the finest carpet cleaning businesses in Bristol. We provide carpet cleaning in Bristol, Bath and the surrounding areas.
Why choose us?
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We pride ourselves on offering the best value for money service, for the best quality carpet cleaning, using the latest and most powerful carpet cleaning machines available, whilst offering the lowest possible prices.
We tailor our cleaning service to the individual customer's needs, whether you want us to clean a multi-story office block or the front room of their home. This approach has built up the Aquadri name to the point where recommendations from satisfied customers represents a large portion of our business; Yes – we even clean entire office blocks purely on recommendations from satisfied customers!
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Aquadri carpet cleaning were contacted to clean the carpets at Bishop primary school, which is the largest primary school in Bristol. During the school summer holiday break, a new heating system had been fitted and the building works required to complete the installation had taken its toll on the carpets. On top of the previous terms daily quota of dairy stains and dust, the carpets were...Read More
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Cannot launch client since update
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Game Clients
FFB Client
Joined: Nov 06, 2013
  Posted: Apr 05, 2017 - 09:22
I run Java 7 on a Ubuntu OS and have played my fair share of BB games here on FUMBBL but it seems like I cannot launch application now since the update. Details are as follows:
Error: Found unsigned entry in resource:
Launch File:
<jnlp spec="1.6+" codebase="https://fumbbl.com/FFBClient/live" href="/ffblive.jnlp?spectate=956477&c=Atari&a=RpJkdyTLnXrFsrJ8e%2FjDDph7cXAHNaPFczVJJUWJovx269qjTUyATrGSCif6chXh">
<update check="always" policy="always"/>
<jar href="FantasyFootballClient.jar"/>
<jar href="FantasyFootballClientResources.jar"/>
<jar href="org.osgi.core-4.3.0.jar"/>
<jar href="tinysound-1.1.1.jar"/>
<jar href="vorbisspi1.0.3.jar"/>
<jar href="jorbis-0.0.17.jar"/>
<jar href="tritonus_share.jar"/>
<j2se version="1.6" href="http://java.sun.com/products/autodl/j2se"/>
<j2se version="1.6+" href="http://java.sun.com/products/autodl/j2se"/>
<application-desc main-class="com.balancedbytes.games.ffb.client.FantasyFootballClient">
com.sun.deploy.net.JARSigningException: Found unsigned entry in resource:
at com.sun.javaws.security.SigningInfo.getCommonCodeSignersForJar(Unknown Source)
at com.sun.javaws.security.SigningInfo.check(Unknown Source)
at com.sun.javaws.security.JNLPSignedResourcesHelper.checkSignedResourcesHelper(Unknown Source)
at com.sun.javaws.security.JNLPSignedResourcesHelper.checkSignedResources(Unknown Source)
at com.sun.javaws.Launcher.prepareResources(Unknown Source)
at com.sun.javaws.Launcher.prepareAllResources(Unknown Source)
at com.sun.javaws.Launcher.prepareToLaunch(Unknown Source)
at com.sun.javaws.Launcher.prepareToLaunch(Unknown Source)
at com.sun.javaws.Launcher.launch(Unknown Source)
at com.sun.javaws.Main.launchApp(Unknown Source)
at com.sun.javaws.Main.continueInSecureThread(Unknown Source)
at com.sun.javaws.Main.access$000(Unknown Source)
at com.sun.javaws.Main$1.run(Unknown Source)
at java.lang.Thread.run(Unknown Source)
Any advice would be appreciated.
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Joined: Aug 02, 2003
  Posted: Apr 05, 2017 - 11:27
FUMBBL Staff
Update to the latest Java from Oracle. Currently, that's Java 8 update 121.
The error you're getting implies that you are lacking a root CA for the certificate used to sign the FFB Client. I'm not sure if the Linux version of Java uses a cetral OS certificate store, but you may need to add the root signing CA certificate to your system as well.
The certificate you need is the Comodo SHA-2 root. I won't link this as it's bad security practice to let other people give you certificates to install. Root CA certificates are quite powerful and installing a bad one can have pretty significant consequences. So you go look it up on your own instead if you end up needing it.
Joined: Nov 06, 2013
  Posted: Apr 06, 2017 - 02:45
Thanks Christer. Have installed Oracle Java and it worked with embedded java code on websites however, I tried to use it on FUMBBL but couldn't get it to interact with the web interface of the FFB client and only advice I could find was to revert back to javaw with the OpenJDK/IcedTea v8. Am having errors with that as well after a full uninstall of all java files and fresh reinstall. (won't load FFB client and has security errors on Java testing site)
Seems to be a problem with security settings but I lack the knowledge to edit the security documents correctly to fix the error (though I have had a look through them). Have spent 5 hours on it the morning but may just wait until I get a computer upgrade, this one is starting to struggle a bit and my knowledge is pretty limited with coding.
If you know how to run a java web interface with Oracle I know I can install that and make it work, enabling firefox to identify it and pass test on javas website but cannot load FUMBBL. Your a busy man, I know, so don't go out of your way just point me in the right direction if it is convenient!
Thanks again
Joined: Aug 02, 2003
  Posted: Apr 06, 2017 - 14:30
FUMBBL Staff
FFB is not going to work properly with OpenJDK/IcedTea. You really do need Oracle's implementation for it to work properly.
You need to make sure your browser loads the jnlp files you download from the site with the javaws executable (note the S on the end, it's important).
But as I said, you may need to update your CA certificate store. With a recent Ubuntu version, that shouldn't be necessary but I have a feeling your machine may have an old release of that as well.
While I do use Ubuntu myself, it's only in a server context. I haven't used linux on the desktop for many many years and it's therefore very hard for me to support your particular setup. Even if I did run Ubuntu on the desktop I'd be running the latest release which you may not be using. While you have a lot of power when running Linux, it's a huge threshold to dive in to what happens behind the scenes.
Either way, my only real recommendation here is to update your Ubuntu to the latest release and make sure you're on Oracle's Java implementation. Security stuff is really hard in general, and without direct access to the machine, I can't help much. It's simply too much stuff that could be wrong and I don't have first-hand experience with desktop Linux in general.
Joined: Nov 06, 2013
  Posted: Apr 07, 2017 - 03:59
Ok, will be able to figure that out. Will update my linux to 16 and hopefully that will solve the issue. I will be able to troubleshoot getting the javaws executable to load I am sure and will switch back to Oracle and will figure out where it has javaws exe as I could only find it in the OpenJDK/IcedT version.
Thanks again for your time Christer, will try my best!
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text:
Event Information
US 23 Country Music Highway Yard SaleHeld the last weekend in May - Thursday, Friday & Saturday
The Yard Sale will begin in Greenup County and follow through all the counties of Highway 23, ending in Letcher County at the Virginia border. Individuals (no commercial vendors please) can set up along Highway 23 with the permission of landowners. No setups will be permitted on the state highway right of way. The Highway 23 Yard Sale will not assume liability for individuals setting up as part of the sale.
4th of July Celebration
Downtown Fireworks Display
Carnival at Archer Park
(606) 886-2336
Hillbilly Arm Drop Drag Racing
Held In May & September
Takes place at Combs Airport, which is located between Prestonsburg & Paintsville.
Battle of Middle Creek Re-enactment & Kentucky Highland Folk Festival
Take a step back in time the second weekend in September at the Middle Creek National Battlefield! Bring an instrument, come and sing, join the fun on the stage, eat good food, enjoy the arts and crafts or simply sit back and relax.
Click here to download a vendor application!
Jenny Wiley Festival
Held the second weekend in October in Downtown Prestonsburg.
Celebrate the heritage of frontier East Kentucky. Live music, carnival, food, arts & crafts, turtle races, a parade, entertainment & much more.
Christmas in the Park
Held at Archer Park
Includes Christmas lights, refreshments, Santa & Mrs. Clause!
Christmas Parade
The Christmas Parade takes place after dark & features lit up parade floats.
(606) 886-2336


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I figured I would continue with the CCP-made cheese theme and decided to talk about the Grand Cru Original King Cuts. My friend, Tiffany Cunningham, who is a CCP that works at the global offices of Whole Foods Market in Austin, TX, had the opportunity to make cheese at Emmi Roth in Monroe, WI. She specifically helped in the making of the King Cuts (along with other yummy Emmi Roth cheeses) which is super exciting because this cheese is only available at Whole Foods Market! Pretty cool right?
Cheese: Grand Cru Original King Cuts
Producer: Emmi Roth Kӓse
Location: Monroe, WI
Milk: Pasteurized cow's milk
Rennet: Microbial (vegetarian)
The Grand Cru Original is a cheese that is made in the style of Gruyere, the Alpine, washed rind cheese from Switzerland. It is super creamy, floral and nutty. Like Gruyere, this cheese is often used as a cooking cheese (think fondue, quiche, or soup), but I really like to feature it on my cheese plate as a cheese that everyone will like. It's very approachable yet still kinda fancy!
I especially love to pair Alpine style cheeses with charcuterie. Today I paired it with some tasty Calabrese salami. The fatty, saltiness of the meat goes perfectly with the rich, creamy Grand Cru Original.
Here are some pictures of Tiffany making the Grand Cru Original... Good work Tiffany, the cheese tastes amazing!
Tiffany cutting and stirring the curd
Here she is washing the Gruyere with a brine solution
If this cheese is tempting your taste buds, be sure to swing by your local Whole Foods Market cheese counter and ask for a taste! You won't be disappointed. Until next time, eat, drink and be happy!!


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Jerry Seinfeld
Jerome Allen "Jerry" Seinfeld born April 29, 1954 is an American comedian, actor, director, writer, and producer.
Seinfeld is best known for portraying a semifictional version of himself in the sitcom, Seinfeld (1989–1998), which he co-created and co-wrote with Larry David. For the final two seasons, Seinfeld and David were co-executive producers.
Seinfeld co-wrote and co-produced the 2007 animated film, Bee Movie, in which he voiced the protagonist. In 2010, he premiered a reality series called The Marriage Ref. He directed Colin Quinn in the Broadway show Long Story Short at the Helen Hayes Theater, which ran until January 2011. He is the creator and host of the web series Comedians in Cars Getting Coffee.
In his stand-up comedy career, Seinfeld is known for specializing in observational comedy, often ranting about relationships and embarrassing social situations.
In 2005 Comedy Central named him the 12th Greatest Stand-up Comedian of All Time.
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Panthers backup quarterback Jimmy Clausen returned to practice on Tuesday, indicating that his recent toe setback wasn't too serious. Then again:
"I still don't feel 100 percent right now," Clausen said via Steve Reed of CarolinaGrowl.com. "The doctor said it's
probably going to be until after the season until I feel 100 percent.
I'm going to have to play through some aches and pains until the season
is over. That's just the nature of football."
Clausen struggled in his second preseason outing against the Jets, but he wasn't any worse than the other quarterbacks who played in the ugliest preseason game of 2010.
Coach John Fox says Clausen has been "very good" thus far and he should continue to get work behind Matt Moore the next two weeks, despite his toe pain.


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Saturday, September 5, 2009
Fake.. Fake... Fake...
India is also not spared from it. As the economy growing tremendously, this needs a lot of regulation in the flow of money to run it smooth. In last couple of years, it is seen that there is a lot of fake currency which is flowing in market. These days lot of transactions happening with the currency having denomination of 500 or 1000. It's easy to carry large amount of cash using Rs.500 or Rs.1000 notes. And most of the fake currency are of denomination 500 only. Sad part is, even ATMs are also vomiting fake currency. The large presence of it has a lot of impact on the economy. This is a kind of threat to the stabilization of the country. There are many rackets which are behind the flow of these currency. Home ministry has admitted that, this is mainly entering indian territory from neighboring countries. Its one kind indirect war with the country to spoil the economy. Reports says that, to manufacture a fake currency of 1000 rupees, it costs around 450 rupees. And it is mostly done in outside india.
RBI also expressed its concerned that, this would help inflation to go up. The other problem to fight for it is, the indian banks has no proper regulations to tap the flow of it. There are cases, even if a person knows that the currency which it is using is fake, she does not go to bank to submit it as in return she does not get anything. As mostly the currency of Rs. 500 or Rs.1000 are seen to be fake, there is an apprehension in the public of loosing that amount, if it is disclosed the money is fake. Hence she uses it continuoly which is a dangerous practise. Sadly there are also instances where the ATM has fake currency. So this indicates the penetration of it and how professionally they are working in spreding this deadly virus.
There is no immediate solution to stop it, but yes it can be minimized by combine effort of Banks, Police and of course Public. Bank should have proper regulation to deal with the fake currency and spreading awareness in the public. Proper reward program and exchage program for fake currency. Passing more information to identify it. Police should be more alert in busting such racket and punishing the culprit, and of course public should me more collaborative in helping these two organization. This is not a ran by a single preson instead done by people who are equally dangerous as terrorist. This is a kind of cancer in the economy and if we want to save ourself, then this can only be cured by collaborative effort by all of us.
5 comments:
Hey in a system where the police work hand in hand with the goons, do you think they can be of any help? The whole system has got corrupted. There are so many things going on which are viruses to our system, but we Indians hav become so resistant to the system that we hav got the attitute "Like we care". Good post anyways... but i guess now its too late to change the system...ReplyDelete
Better to be late than never.ReplyDelete
The system starts with us. So atleast we can try instead of being numb.
why don't u add some tips on identifying fake currency that is running currently..I heard there is some series that is fake...this willl help people being safe..Nice blog..keep coming..ReplyDelete
I was victim once in a bank. I also really don't know how to identify it. The shopkeepers are the people who identifies it quickly and are better than bankers. We should learn from them.ReplyDelete


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Friday, 12 June 2015
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The answer ~ Q-tips, bar soap, coffee filters, garbage bags …
The question ~ What are the things you ALWAYS forgot at the store?
A simple idea that we have been using here at SbS HQ to avoid the trip back to the store …
If you take the last of anything, or preferably the 2nd to last … tear off a piece of the box, bag, packaging and leave it out where we make the shopping lists.
What simple tricks, or ideas, do you use to make it all work?
~ Peace


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To elucidate the biological role of Stat3 in the skin, conditional gene targeting using the Cre‐loxP system was performed as germline Stat3 ablation leads to embryonic lethality. K5‐Cre;Stat3flox/− transgenic mice, whose epidermal and follicular keratinocytes lack functional Stat3, were viable and the development of epidermis and hair follicles appeared normal. However, hair cycle and wound healing processes were severely compromised. Furthermore, mutant mice expressed sparse hair and developed spontaneously occurring ulcers with age. Growth factor‐dependent in vitro migration of Stat3‐disrupted keratinocytes was impaired despite normal proliferative responses. We therefore conclude that Stat3 plays a crucial role in transducing a signal required for migration but not for proliferation of keratinocytes, and that Stat3 is essential for skin remodeling, including hair cycle and wound healing.
STATs (signal transducers and activators of transcription) belong to a family of cytoplasmic proteins that are activated by a large number of extracellular signaling molecules including cytokines, growth factors and hormones (Schindler and Darnell, 1995; Ihle, 1996; Darnell, 1997; O'Shea, 1997). Activation of STATs is accomplished by their phosphorylation on a tyrosine residue mediating their dimerization through reciprocal Src homology 2 (SH2) phosphotyrosine interactions, leading to nuclear translocation and hence transcriptional regulation of target genes. STATs are phosphorylated either by receptor tyrosine kinases such as receptors for epidermal growth factor (EGF), platelet derived growth factor (PDGF) and colony‐stimulating factor‐1 (CSF‐1), or by Janus kinases (JAKs) which are non‐covalently associated to receptors. Cytokine receptors lacking an intrinsic kinase activity mediate signals to STATs through the activation of JAKs.
Seven STATs have now been identified in mammals: Stat1, Stat2, Stat3, Stat4, Stat5A, Stat5B and Stat6. Each of these Stats is differentially activated by various extracellular ligands, thereby allowing differential intracellular processing of signals transduced across the membrane. The biological role of each of the Stats has been delineated by investigating the phenotype of mice deficient for each individual Stat. Innate immune responses to viral or bacterial infections were impaired in Stat1 mutant mice, reflecting its role in mediating the action of interferon (Durbin et al., 1996). Stat4 is activated in T cells by IL‐12 stimulation, which leads to development of T helper‐1 (TH1) cells. Stat4 knockout mice are accordingly deficient in TH1 function (Kaplan et al., 1996). On the other hand, Stat6 knockout mice have deranged IL‐4 signaling and cannot generate a TH2 response (Takeda et al., 1996). Whereas Stat4 and Stat6 are activated by a limited number of ligands, Stat5A and Stat5B have a broad activation profile by various ligands including prolactin, growth hormone, erythropoietin, granulocyte‐macrophage colony‐stimulating factor and IL‐2. Stat5A knockout mice, however, develop normally except for the inability of females to lactate after parturition because of a failure in mammary gland differentiation (Liu et al., 1997). Stat5B knockout mice show a phenotype related to growth hormone signaling (Udy et al., 1997).
Stat3 is activated by cytokines of the IL‐6 family such as IL‐6, Il‐11, leukemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), oncostatin M and cardiotropin 1 (reviewed by Akira, 1997). Non‐cytokine ligands such as EGF, PDGF, hepatocyte growth factor (HGF), granulocyte colony‐stimulating factor (G‐CSF) and leptin have also been shown to activate Stat3 (Darnell 1997; Boccaccio et al., 1998). The phenotype of Stat3 knockout mice is unique in that it leads to an early embryonic lethality (Takeda et al., 1997). Thus, the absence of Stat3 is not compensated for by any other Stats expressed in the visceral endoderm during 6.5 and 7.5 days of development. We envisage that Stat3 may be spatio‐temporally activated by certain combinations of ligands and receptors. Because embryonic lethality ensues in Stat3‐null mice generated by conventional gene targeting technology, a conditional, tissue‐specific and/or temporal, gene knockout strategy was required for assessing its later biological role. Takeda et al. (1998, 1999) have recently generated Stat3 knockout mice specifically in T lymphocytes or in macrophages/ neutrophils by using a Cre‐loxP strategy (Rajewsky et al., 1996), and delineated distinct roles of Stat3 for the respective cell lineage.
The growth and differentiation of keratinocytes is regulated by many growth factors and cytokines including EGF, transforming‐growth factor (TGF)‐α, heparin binding EGF‐like factor (HB‐EGF), amphiregulin, keratinocyte growth factor (KGF), TGF–β, insulin‐like growth factor, PDGF, HGF, IL‐6, IL–1 and TNF‐α (reviewed by Bennett and Schultz, 1993; Peus and Pittelkow, 1996; Martin, 1997). EGF receptor (R) knockout mice demonstrated an abnormality in skin structure and hair development (Miettinen et al., 1995; Murillas et al., 1995; Sibilia and Wagner, 1995). A similar phenotype in skin and hair was observed in TGF–α knockout mice (Luetteke et al., 1993), suggesting that TGF–α, an autocrine growth factor of the EGF family (Coffey et al., 1987), plays a crucial role in skin development. Interestingly, Stat3 is activated by factors of the EGF family as well as by HGF, PDGF or IL‐6 (Zhong et al., 1994; Akira, 1997; Boccaccio et al., 1998), which are all involved in growth/differentiation of keratinocytes (Rheinwald and Green, 1977; Grossman et al., 1989; Matsumoto et al., 1991; Martin, 1997). Successful ablation of a floxed Stat3 allele using Cre recombinase driven by keratin 5 promoter allowed us to generate keratinocyte‐specific Stat3 knockout mice. A comprehensive analysis of skin development as well as wound healing and hair cycling in these keratinocyte‐specific Stat3‐null mice revealed that Stat3 plays pivotal roles in skin remodeling.
Stat3 deficiency in keratinocytes of K5‐Cre;Stat3flox/− mice
To elucidate the physiological role of Stat3 in the skin, we specifically disrupted the Stat3 gene in keratinocytes by crossing Stat3flox mice (Takeda et al., 1998) with keratin5‐Cre transgenic mice (K5‐Cre) (Tarutani et al., 1997). The keratin 5 promoter directs gene expression in the basal layer of epidermal and follicular keratinocytes, so that a floxed gene is disrupted throughout the epidermis and outer root sheath of hair follicles (Byrne and Fuchs, 1993; Murillas et al., 1995; Tarutani et al., 1997). To increase the efficiency of Cre‐mediated Stat3 disruption and prevent Cre‐mediated inter‐chromosomal recombination, a Stat3‐null allele was introduced over the floxed allele (Takeda et al., 1997, 1998). Genotyping of Stat3 gene for both alleles was carried out by genomic PCR (Figure 1A) and the efficiency and specificity of the Cre‐mediated Stat3 disruption was determined (Figure 1B). As previously described in floxed Pig‐a gene in K5–Cre mice (Tarutani et al., 1997), disruption of floxed Stat3 in K5‐Cre;Stat3flox/− mice was efficient and specific in keratinocytes. Keratinocytes from Stat3‐disrupted mice expressed a reduced amount of Stat3 protein whose relative molecular mass was slightly decreased (Takeda et al., 1998), corresponding to the truncated Stat3 (Stat3Δ) (Figure 1C). Stat3Δ together with wild‐type Stat3 was detected in keratinocytes from K5‐Cre;Stat3flox/+ mice (Figure 1C). Reverse transcriptase (RT)–PCR and DNA sequencing analysis revealed that Stat3Δ lacks the tyrosine residue essential for phosphorylation and the MAP‐kinase recognition site (Takeda et al., 1998), both of which are critical for Stat3 activation (Zhang et al., 1995).
Inability of Stat3 activation in K5‐Cre;Stat3flox/− keratinocytes
Stimulation with EGF gave rise to Stat3 phosphorylation in the keratinocytes of Stat3flox/+ and K5‐Cre;Stat3flox/+ but not of K5‐Cre;Stat3flox/− mice (Figure 2A). Additionally, Stat3Δ in K5‐Cre;Stat3flox/+ keratinocytes did not induce a dominant‐negative effect on wild‐type Stat3 phosphorylation. This contrasts with the finding that wild‐type Stat3 was inhibited by Stat3Δ in thymocytes of Lck‐Cre; Stat3flox/+ mice (Takeda et al., 1998).
Immunohistochemical analysis with an anti‐Stat3 antibody revealed that in wild‐type keratinocytes, Stat3 was clearly translocated to the nucleus after EGF or HGF stimulation (Figure 2B). However, it should be noted that enhanced immunoreactivity to the anti‐Stat3 antibody was simultaneously observed in the activated wild‐type keratinocytes. On the other hand, Stat3 was weakly stained in keratinocytes of K5‐Cre;Stat3flox/− mice irrespective of the stimulation, corresponding to the result of Western blotting shown in Figure 1C, in which the amount of Stat3Δ appeared to be reduced.
Skin development is intact in K5‐Cre;Stat3flox/− mice
Despite functional ablation of Stat3 in the keratinocytes of K5‐Cre;Stat3flox/− mice, these mice were viable and displayed no developmental alterations in the epidermis and hair follicles by postnatal day 11 (PD11) (Figure 3). Histologically, the structure of horny, spinous and basal cell layers of the epidermis were similar and devoid of any abnormality in these Stat3‐disrupted mice. Such Stat3‐disrupted mice also showed no gross alterations in the length and texture of the first coat of skin (data not shown). Growth and differentiation markers of keratinocytes such as keratin 6, 10, 14 and involcrin were appropriately expressed in the epidermis and hair follicles (data not shown).
Impairment of the second hair cycle in Stat3–disrupted mice
Because Stat3 is disrupted in keratinocytes of the outer root sheath, the hair cycle in Stat3‐disrupted mice was examined. Hair follicles elongate to reach the deep adipose tissue at the anagen stage (Figure 3, PD11), then undergo gradual cellular quiescence (catagen) and finally, around PD19 undergo complete rest (telogen). Until this stage there was no observed difference between control littermates and Stat3‐disrupted mice. However, the second anagen was not observed in the mutant mice (Figure 3, right panel of PD28). In contrast, the control mice entered the anagen, expressing thickened and elongated hair follicles far down into the adipose tissue (Figure 3, left panel of PD28). Stat3‐disrupted mice remained in a telogen stage even by PD35 when the control littermates were at the late anagen stage. It is interesting to note that at this stage the Stat3‐disrupted skin displayed pronounced dermal fibrosis together with infiltration of inflammatory cells and an atrophic change in adipose tissue. Thus, we suggest that Stat3 regulates the second and subsequent hair cycles whereas the first hair cycle, which starts around 14.5 days post coitus (d.p.c.) (Kashiwagi et al., 1997), is Stat3 independent.
Retardation of skin wound healing in Stat3–disrupted mice
Stat3‐disrupted and control littermates were wounded with a biopsy punch and then the process of healing was monitored. Wound healing was markedly retarded in the Stat3‐disrupted mice while re‐epithelialization was completed in the control littermates on day 8 after excision wounding (Figure 4A). Histological examination revealed an ulcer of the skin in the Stat3‐disrupted mice, whereas at this time point the wound had completely healed in the control littermates (Figure 4B). However, no difference was shown between the Stat3‐disrupted and control mice in the dermal responses to wound such as granulation, inflammation and neovascularization. Thus the retarded wound healing in the Stat3‐disrupted mice was due not to an impairment in secondary development of dermal components but rather to a fault in epidermal regeneration.
To evaluate quantitative differences in the wound healing process, wound diameter was sequentially measured. Wild‐type, K5‐Cre transgenic Stat3flox/+ (referred to as +/+) and K5‐Cre;Stat3flox/+, Stat3xflox/− (+/−) mice had completely healed by 10 days after wounding (Figure 3C). At the same time point, the wound in K5‐Cre;Stat3flox/− mice (−/−) was still open (average wound 4 mm), and usually healed at ∼20 days after wounding (Figure 3C).
Disruption of the floxed Stat3 allele occurred in a keratinocyte‐specific manner (Figure 1B and C) with very little, if any, disruption in epithelial cell‐containing organs such as stomach and oesophagus (Tarutani et al., 1997). Thus, it is possible that the retarded wound healing in K5‐Cre;Stat3flox/− mice might be due to disruption of Stat3 in other tissue(s). In order to exclude this possibility and to confirm that the primary cause of the retarded wound healing in the Stat3‐disrupted mice was impaired regeneration of the epidermis, the skin was transplanted on to nude mice. The retarded phenotype was reproduced in the Stat3‐disrupted skin (Figure 3D), compounding the idea that the primary cause of retarded wound healing in the Stat3‐disrupted mice resides within the mutant skin itself.
Although retarded, wound healing was eventually completed in the K5‐Cre;Stat3flox/− mice (Figure 3C). It should be noted that dermal contraction could draw the wound edges together (Martin, 1997), and hence contribute to wound closure in these mice.
Migration defect of the Stat3‐disrupted keratinocytes accounts for the phenotype
Cell migration and proliferation are critical events in re‐epithelialization of cutaneous wounds (reviewed by Bennett and Schultz, 1993; Martin, 1997) and hair growth (reviewed by Peus and Pittelkow, 1996). Therefore, the motility and growth of keratinocytes in vitro were examined in the Stat3‐deficient keratinocytes. In vitro wounds were inflicted in subconfluent keratinocyte cultures pretreated with mitomycin C to prevent cell proliferation. Following wounding, closure of the cell‐free area by migrating cells was examined in the presence of EGF, TGF–α, HGF, IL‐6 and keratinocyte growth factor (KGF), all of which have been reported to promote epithelial cell motility (Barrandon and Green, 1987; Matsumoto et al., 1991; Nishida et al., 1992; Werner et al., 1994; Sato et al., 1995). EGF, TGF–α, HGF and IL‐6, all of which activate Stat3 (Figure 2, and Zhong et al., 1994; Boccaccio et al., 1998), promote the migration of Stat3+/− keratinocytes (Stat3flox/−) (Figure 5A). In contrast, the migration of Stat3‐disrupted keratinocytes was severely impaired in the presence of these ligands (Figure 5A). KGF, a paracrine stimulator for keratinocyte migration as well as proliferation (Werner et al., 1994; Sato et al., 1995), did not activate Stat3 in keratinocytes (data not shown) nor promote the migration of keratinocytes from either control or Stat3‐disrupted mice (Figure 5A). Our results support the finding that KGF acts as a mitogen, and not a migration stimulator for keratinocytes (McCawley et al., 1998). Figure 5B demonstrates a quantitative difference of ligand‐dependent migration between the control and Stat3‐disrupted keratinocytes. Thus, functional Stat3 is required for the migration and accordingly re‐epithelialization of keratinocytes.
The involvement of Stat3 in keratinocyte proliferation was also examined. Growth factor‐dependent proliferation of the Stat3‐disrupted keratinocytes in vitro was appreciable and comparable to the control in terms of dose dependency of exogenous ligands (Figure 5C). Ki67, which is a proliferation‐associated antigen (Gerdes et al., 1983), was expressed in keratinocytes at the wound edge and hair follicles of Stat3‐disrupted as well as control mice in vivo (data not shown). Thus, keratinocyte proliferation is mediated through Stat3‐independent pathway(s). Taken together, the retarded in vivo wound healing in the K5‐Cre;Stat3flox/− mice could be attributed to the poor motility of Stat3‐disrupted keratinocytes.
Spontaneous skin alterations in aged Stat3–disrupted mice
Despite the normal appearance of the skin in Stat3‐disrupted mice at birth, Stat3‐disrupted mice older than 2 months had sparse hair and developed scale and crusts on an apparently rough skin surface (Figure 6A). Histologically, they harbored spontaneous ulcers and erosions with a decreased number of hair follicles (Figure 6B). Additionally, the mutant mice expressed marked hyperplasia of the epidermis (acanthosis) with hyperkeratosis and scale‐crusts. There was pronounced inflammatory infiltration and fibrosis throughout the dermis. While most of the hair follicles were at the telogen phase, some were at anagen. Furthermore, there were aberrant hair follicles; for example, small clusterings of matrix cells, which resembled undifferentiated hair germs (Figure 6C), distorted or curved hair shafts (Figure 6D) or gigantic hair bulbs with bizarre shapes (Figure 6E). The phenotype expressed in aged Stat3‐disrupted mice appears to be consequent to the impaired wound healing and disorganized hair cycling. Thus Stat3 plays a crucial role in the remodeling of the skin and hence in the structural integrity of the tegument in mice.
STATs are latent cytoplasmic proteins that deliver signals from extracellular stimuli to the nucleus in order to regulate the transcription of many different genes (reviewed by Schindler and Darnell, 1995; Ihle, 1996; Darnell, 1997; O'Shea, 1997). Despite complexity in the determination of STAT availability for specific cell lineages, phenotypes revealed through the knockouts of specific STAT family member highlight their predominant biological functions in vivo. Stat3 is activated by a number of ligands including IL‐6‐type cytokines (IL‐6, CNTF, LIF, oncostatin M, Il‐11, cardiotropin 1) and EGF, PDGF, HGF, G‐CSF, IFN‐α/β, IL‐2, IL–10, CSF‐1, angiotensin II, leptin, erythropoietin and thrombopoietin (Akira, 1997). Knockout of Stat3 in the germline results in embryonic lethality (Takeda et al., 1997), implying that Stat3 has global and critical effects on development. Therefore, conditional gene targeting in the specific lineage was required for assessing its later biological roles.
Cre‐loxP system enables analysis of Stat3 function in keratinocytes
The Cre‐loxP system used here specifically removes the tyrosine phosphorylation site together with the mitogen‐activated protein kinase (MAPK) recognition site (Takeda et al., 1998), both of which are important for Stat3 activation (Zhang et al., 1995). Using the Cre‐loxP system with the same floxed Stat3 construct, Takeda et al. (1998) have recently established mice that have specifically ablated Stat3 in T cells or macrophages/neutrophils. T cells from Lck‐Cre;Stat3 flox/− mice do not proliferate in response to IL‐6 probably because these T cells are unable to prevent apoptosis upon IL‐6 stimulation. Mice devoid of Stat3 in macrophages/neutrophils developed chronic enterocolitis revealed by skewed Th1 predominance because of a lack of IL–10 production (Takeda et al., 1999). In the present study, keratinocytes devoid of Stat3 failed to respond to EGF, HGF or IL‐6, resulting in their impaired migration (Figure 5A and B). Thus, in contrast to the outcome of gene targeting of a Stat family member having a narrow activation profile such as Stat6, the Stat3 knockout results in various alterations in a cell‐lineage‐specific fashion.
The basal layer of the epidermis expresses keratin 5 (K5) which pairs with K14. When keratinocytes differentiate from basal to spinous cells, the expression of K5/K14 decreases and that of K1/K10 is initiated. K5 is also expressed in the outer root sheath cells of hair follicles (Byrne and Fuchs 1993), namely follicular keratinocytes. In K5‐Cre;Stat3flox/− mice, Stat3 would therefore be disrupted throughout the epidermis and outer root sheath of hair follicles. The alteration of hair architecture in these mice is likely to be due to the lack of Stat3 in the outer root sheath cells.
Disruption of the EGFR by homologous recombination (Miettinen et al., 1995; Sibilia and Wagner, 1995), or by introducing a dominant‐negative mutant as a transgene in mice under the control of the K5 promoter (Murillas et al., 1995), demonstrates rudimentary curly whiskers and waved pelage hair. The hair follicles in these mice fail to enter into the catagen phase, and are arrested at the anagen stage. In organ cultures of embryonic skin, exogenous EGF inhibited the formation of hair follicles at an early stage in the development of hair rudiments (Kashiwagi et al., 1997). Administration of excessive doses of EGF to newborn mice cause follicles to enter catagen phase (Moore et al., 1981). Taken together, these data suggest that EGFR signaling controls hair follicle morphogenesis and subsequent hair cycles through an inhibitory effect on the growth of hair follicles. The observation that EGFR expression is down‐regulated at the tip of the migrating front of embryonic hair germ and anagen follicles (Green and Couchman, 1984) may, therefore, account for this machinery being refractory to growth factors of the EGF family.
In contrast, the hair follicles of keratinocyte‐specific Stat3‐disrupted mice develop normally, with the first hair cycle being normal (Figure 3, PD11, PD19). Thus an EGFR signal independent of the Stat3 pathway is required for the organized morphogenesis of hair follicles and induction of catagen. Despite the normal appearance of the first hair cycle, Stat3‐disrupted mice are impaired at the onset of the second anagen (Figure 3, PD28). Since the EGFR is absent from the tip of the migrating front of early second anagen follicle (Green and Couchman, 1984), we suggest that Stat3 activation by ligands other than EGF family members is required at this phase. Among a wide variety of ligands which activate Stat3, HGF is the most likely candidate due to the fact that exogenous HGF accelerates and prolongs the anagen phase of hair follicles (Jindo et al., 1998). Although the hair follicles in Stat3‐disrupted mice remain in telogen at PD35, some of the follicles can enter anagen with age (Figure 6B). Interestingly, the aged follicles are less synchronized and are of an unusual shape (Figure 6C–E). Growth factor(s) whose downstream signals bypass Stat3 could induce anagen albeit less efficiently. During this interruption of the hair cycle, the dermis is thickened with fibrosis and the subcutaneous adipose tissue is replaced by granulomatous tissue resulting in atrophic change (Figure 3, PD28, PD35). Similar alterations in the dermis occurred in mice with EGFR deficiency acquired by transgenesis of a dominant‐negative mutant driven by the K5 promoter (Murillas et al., 1995). This implies the presence of pathological epithelium–mesenchyme interactions in the hair follicle (Hardy, 1992).
A migration defect in Stat3‐disrupted keratinocytes is responsible for impaired skin remodeling
We found that wound healing in keratinocyte‐specific Stat3‐disrupted mice is retarded not only in vivo (Figure 4) but also in vitro (Figure 5A and B), such that keratinocyte migration under the stimulation of growth factors is severely compromised, despite the proliferative response appearing normal (Figure 5C). During skin wound healing, epidermal keratinocytes at the wound edge are stimulated by a wide variety of cytokines and growth factors that promote keratinocyte migration and proliferation, resulting in re‐epithelialization (reviewed by Bennett and Schultz, 1993; Martin, 1997). Members of the EGF family, especially TGF‐α (Coffey et al., 1987) and HB‐EGF (Higashiyama et al., 1991), play a pivotal role in stimulating epidermal keratinocytes in the wound in an autocrine or juxtacrine fashion, respectively. HB‐EGF‐dependent migration was also compromised in Stat3‐disrupted keratinocytes (data not shown), suggesting that Stat3 mediates a signal through HER4 as well as HER1. HER4 is activated by HB‐EGF; HER4 activation stimulates chemotaxis but not proliferation (Elenius et al., 1997). IL‐6 and HGF also activate Stat3, and can promote epithelial cell growth or migration in vitro (Grossman et al., 1989; Matsumoto et al., 1991). These cytokines may be generated from wound‐associated mesenchymal cells such as activated fibroblasts or macrophages, and therefore stimulate keratinocyte migration in vivo. Since wound closure did occur eventually in K5‐Cre;Stat3flox/− mice (Figure 4C), we suggest that intracellular signaling molecule(s) other than Stat3 may also be involved in keratinocyte migration in vivo. Furthermore, the Stat3 pathway has also been shown to cooperate with other intracellular signaling pathways such as ras‐MAP kinase to promote epithelialization (Boccaccio et al., 1998).
Cell adhesion to extracellular matrix (ECM) components and their degradation by proteolytic enzymes play important roles in tissue remodeling (Yuspa et al., 1993; Martin, 1997). Growth factors could co‐ordinate keratinocyte function in integrin expression and production of proteases such as matrix metalloproteinases (MMPs) during the process of skin remodeling (Yuspa et al., 1993; Peus and Pittelkow 1996; Martin, 1997). Keratinocyte migration requires MMP production in order to degrade ECM components. Recent studies have revealed that EGF or HGF trigger keratinocytes to produce collagenase‐1 (Dunsmore et al., 1996; Pilcher et al., 1997) and MMP‐9 (McCawley et al., 1998). Transcriptions of MMP13 (murine homologue to collagenase‐1) and MMP9 in Stat3‐disrupted and control keratinocytes were enhanced by EGF or HGF (data not shown), suggesting that Stat3 is not involved in promoting the transcription of these protease genes. α2 integrin forms a heterodimeric receptor with β1 integrin specific for type‐I collagen (Chen et al., 1993). However, we obtained no difference in EGF‐upregulated α2 integrin expression between Stat3‐disrupted and control keratinocytes (data not shown). We cannot exclude the possibility that Stat3‐disrupted keratinocytes are compromised in the expression of integrins other than α2 or in subsequent signaling after binding to specific ECM molecules essential for migration.
Since epidermal and follicular keratinocytes (outer root sheath cells) share features (Lenoir et al., 1988; Byrne and Fuchs, 1993), it is likely that hair cycle impairment in Stat3‐disrupted mice is also due to a failure in the migration of follicular keratinocytes. Indeed, an anagen progression involves downward migration of hair follicle keratinocytes responding to an as yet undefined 'dermal message' (Hardy, 1992).
Morphogenesis and remodeling in the skin
In 14.5 d.p.c. mice embryonic skin, the pilosebaceous units develop from epidermal downgrowths (Kashiwagi et al., 1997) under the influence of specific mesenchymal cell condensations, which supply permissive and instructive signals that govern the position and type of hairs and other appendages (reviewed by Hardy, 1992; Stenn et al., 1996). These signals are regulated by the expression of patterning genes, such as Wnt‐catenin‐LEF‐1 signaling (Gat et al., 1998), sonic hedgehog (St‐Jacques et al., 1998), bone morphogenetic protein families (Blessing et al., 1993) and many others (reviewed by Stenn et al., 1996), leading to development of hair buds. Since K5 is expressed in the epithelia earlier than the onset of hair morphogenesis (Ramirez et al., 1994), the Stat3 gene must be disrupted in outer root sheath throughout the developing processes. Moreover, we found that disruption of Stat3 was almost complete in neonatal keratinocytes from K5‐Cre;Stat3flox/− mice (Figure 1B). Thus, Stat3 in keratinocytes is not involved in the morphogenesis of skin and hair follicle since keratinocyte‐specific Stat3‐disrupted mice show no anomalies at birth. It is highly likely that compromised migration of Stat3‐disrupted keratinocytes is responsible for the failure to enter the ordered second anagen which is initiated by the dermal mesenchymal signal, namely cytokines/growth factors emanating from dermal papilla (Hardy, 1992; Stenn et al., 1996). Data presented here are in agreement with the concept that the first hair cycle is distinct from all the subsequent hair cycles in its cellular origin and morphological sequence, such that the first hair cycle might be regarded as a neogenic event (Wilson et al., 1994). Taken collectively, these observations suggest that Stat3 activation is indispensable for the progression of the second hair cycle onwards, which represents one of remodeling phases of the skin, although the morphogenesis of hair follicles is independent of Stat3. Based on this, a hypothetical model of the hair cycle is depicted in Figure 7.
Throughout life, epidermal keratinocytes continuously grow, differentiate and die. Keratinocytes are provided from stem cells located in the interfollicular epidermis and in a bulge region of the lower outer root sheath of the follicles (Cotsarelis et al., 1990). Spontaneous wounds and sparse hair development in the aged Stat3‐disrupted mice (Figure 6A and B) may be due to an inability of bulge‐derived stem cells to migrate and serve as new stem cells at the wound site and in the outer root sheath. Stem cells in the latter may be necessary to form organized anagen follicles. Thus keratinocyte Stat3 appears to play a critical role in the process of skin homeostasis and remodeling. This role in skin remodeling recapitulates its involvement in liver regeneration, where IL‐6, EGF‐family members and HGF, all of which activate Stat3, increase in the serum after partial hepatectomy. These cytokines are essential for liver regeneration (Michalopoulos and DeFrances, 1997). In conclusion, Stat3 contributes significantly to keratinocyte activity especially in skin remodeling including wound healing and hair cycling processes.
Materials and methods
Generation of gene targeting mice using Cre‐loxP strategy and PCR
Generation of K5‐Cre transgenic mice (Tarutani et al., 1997), Stat3‐null heterozygous mice (Takeda et al., 1997) and Stat3flox/flox mice (Takeda et al., 1998) were previously described. K5‐Cre transgenic mice were bred with Stat3‐null heterozygous mice to generate mice carrying the K5‐Cre transgene and a Stat3‐null allele (K5‐Cre;Stat3+/−). These mice were then mated with Stat3flox/flox mice. Offspring carrying a floxed Stat3 allele and/or K5‐Cre transgene (K5‐Cre;Stat3flox/+, K5‐Cre;Stat3flox/−, Stat3flox/+, Stat3flox/−) were used for further analyses. Allele‐specific PCR was carried out as illustrated in Figure 1A. The primers used, 'a' (5′‐CCTGAAGACCAAGTTCATCTGTGTGAC‐3′), 'b' (5′‐CACACAAGCCATCAAACTCTGGTCTCC‐3′) and 'c' (5′‐GATTTGAGTCAGGGATCCTTATCTTCG‐3′) are specific for exon 21, exon 22 of the Stat3 gene and the 5′ loxP site of the targeted construct, respectively. Using a mixture of these primers, PCR was performed with 35 cycles of a reaction consisting of 1 min of denaturation at 93°C, 1 min of annealing at 65°C and 2 min of elongation at 72°C. With primers 'a' and 'b', PCR products were ∼250 and 350 bp specific for wild‐type, and floxed Stat3 allele, respectively. With primers 'b' and 'c', they were 150 bp specific for the Stat3Δ allele.
Preparation of keratinocytes
Full‐thickness skin taken from newborn to 5–day‐old mice was treated with 250 U/ml of dispase (Godo Shusei, Tokyo, Japan) overnight at 4°C, and the epidermis was peeled off from the dermis and trypsinized in order to yield single cells. It should be noted that epidermal keratinocytes prepared by this method are inevitably contaminated with follicular keratinocytes from outer root sheath (Kitano and Okada, 1983). Mice were killed by intraperitoneal injection of sodium pentobarbital.
Western blotting
Keratinocytes of equivalent numbers or liver tissue of equivalent wet weight was lysed with ice‐cold lysis buffer containing 0.5% Nonidet P–40, 10 mM Tris–HCl pH 7.4, 150 mM NaCl, 1 mM EDTA, 0.2 mM phenylmethylsulfonyl fluoride, 1 mM NaVO3 and 5 μg/ml aprotinin. Whole‐cell lysates were incubated with anti‐Stat3 (C‐20; Santa Cruz Biotechnology, Santa Cruz, CA) followed by protein G–Sepharose (Pharmacia, Uppsala, Sweden) overnight at 4°C. Immunoprecipitates were separated on SDS–polyacrylamide gel, transferred to a nitrocellulose membrane and blotted with the same antibody, followed by treatment with horseradish‐peroxidase‐conjugated anti‐rabbit immunoglobulin (Amersham, Buckinghamshire, UK), and then visualized with an enhanced chemiluminescence (ECL) system (Amersham). To examine the phosphorylation of Stat3, keratinocytes were cultured in MCDB153 medium (Kyokuto, Tokyo, Japan), supplemented with 5 μg/ml insulin, 0.1 mM monoethanolamine, 0.1 mM phosphoryl ethanolamine and 0.5 μM hydrocortisone at 37°C under an atmosphere with 5% CO2, and allowed to grow for 3 days in the presence of 1% bovine pituitary extract (BPE, prepared by mincing of bovine pituitary glands). After starvation for 24 h, cells were treated with or without 100 ng/ml EGF (Upstate Biotechnology, Lake Placid, NY) for 20 min, subject to cell lysis. Cell lysates of epidermal keratinocytes of equivalent numbers were subjected to Western blotting as described above, except that anti‐phosphorylated Stat3 (Tyr705; New England Biolabs, Beverly, MA) was used for blotting.
Immunocytochemical staining
Keratinocytes were treated with or without 100 ng/ml EGF or HGF (Collaborative Biolamedical Products, Bedford, MA) for 40 min. They were fixed with 4% paraformaldehyde for 10 min, permeabilized with 0.3% Triton X‐100 for 5 min and incubated with anti‐Stat3 (C‐20; Santa Cruz Biotechnology), followed by treatment with biotinylated anti‐rabbit IgG and horseradish‐peroxidase‐conjugated ABC reagent (Vector Laboratories, Buringame, CA).
Wound healing assay
These experiments were carried out with strict adherence to institutional guidelines for minimizing distress in experimental animals. Under anesthesia with sodium pentobarbital, full‐thickness skin excisions were made on the back of 6‐ to 9‐week‐old mice using a biopsy punch of 6 mm diameter. In graft experiments, pieces of full‐thickness skin (2–3 cm2) obtained from mice of indicated genotypes were transplanted on to the back of Balb/c nu/nu mice (10‐week‐old), whose back skin had been ablated with a razor and then fixed tightly with adhesive bandages for a week. Two weeks after transplantation the grafted skin was wounded with a biopsy punch of 4 mm diameter. The punched‐out grafted skin was subject to PCR to confirm the donor's genotype.
In vitro migration assay
Keratinocytes were cultured in dishes precoated with type‐I collagen (Iwaki Glass, Tokyo, Japan) until they reached subconfluency in the presence of BPE, then starved for 24 h, treated with 10 μg/ml mitomycin C for 2 h to avoid the proliferative effect on the cells and finally subjected to in vitro wound closure assay. A cell‐free area was introduced by scraping the monolayer with a yellow pipette tip. Cell migration to the cell‐free area for another 48 h was evaluated in the absence of exogenous ligands or in the presence of 30 ng/ml EGF, TGF‐α (Otsuka Pharmaceutical, Tokushima, Japan), HGF, KGF (PeproTech, London, UK) and IL‐6 (R&D Systems, Minneapolis, MN). Photographs were taken using a phase‐contrast microscope (DIAPHOT 300; Nikon, Tokyo, Japan). The number of migrating keratinocytes were counted after taking photographs of four non‐overlapping fields. Values represent the mean ± SE of migrating cells per mm2 beyond the frontiers of the in vitro wound edge.
Proliferation assay
Keratinocytes (104) were plated in a well of a 96‐well type I collagen‐precoated plate (Iwaki Glass), and cultured in the presence of EGF or HGF at the concentrations indicated for 72 h. They were pulsed with 0.5 μCi [3H]thymidine (Amersham) for the final 8 h of the culture, and then precipitated with trichloroacetate, and radioactivity was measured by a γ‐scintillation counter.
We thank Drs T.Hirano, K.Hadjantonakis and S.Joyce for reading of the manuscript, and Mrs S.Okamoto for excellent technique for immunocytochemical and immunohistochemical studies. This work was supported by grants of the Ministry of Education, Science and Culture of Japan (#10670787), and in part by CREST of Japan Science and Technology Corporation. Care of experimental animals was in accordance with the institutional guidelines.
- Copyright © 1999 European Molecular Biology Organization


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PAPER REVIEW: Man Utd's Rooney fears axe, Campbell's Arsenal future, Koeman to Saints
ENGLAND striker Wayne Rooney fears that he could be dropped for England's crucial World Cup group match against Uruguay. Arsenal boss Arsene Wenger will give Costa Rican striker Joel Campbell a chance at the Emirates next season. Ronald Koeman will be appointed as Mauricio Pochettino's replacement at Southampton in the next few days.
Wayne Rooney fears he could be dropped for England's crucial World Cup match against Uruguay.
The United striker failed to impress against Italy on Saturday night and his poor performance has led many to question his place in Roy Hodgson's side.
Arsene Wenger will give Joel Campbell a chance to prove himself at Arsenal next season.
Campbell, 21, impressed in Costa Rica's shock 3-1 victory over Uruguay on Saturday, and Gunners boss Arsene Wenger has confirmed that he will play the in-form striker next season.
Southampton will replace Mauricio Pochettino with former Ajax boss Ronald Koeman.
The Dutchman has reportedly agreed a three year contract at St Mary's and will be unveiled in the next few days.


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Islam is not just a set of religious beliefs. It is an all-encompassing identity. It is inconceivable to change that identity, even for those who barely practice their Islamic faith. To do so is like suicide. It kills the identity of the convert and leaves the rest of the family in a state of shameful mourning.
Nabeel Qureshi has given us, I think, not only an outstanding memoir of conversion to Christianity from the Islamic faith, but a formidable work of apologetics, in his book Seeking Allah, Finding Jesus. It makes an excellent companion work to Lee Strobel's The Case for Christ (indeed, Strobel provides the introduction to this expanded edition).
If you're expecting a story of a man who longed for freedom from Islamic bondage and found it at last, you will be disappointed here. Nabeel Qureshi is more like C.S. Lewis, "dragged kicking and screaming" into Christianity, a "most reluctant convert."
Nabeel was raised in a loving, even somewhat indulgent home of Muslims of the Ahmadi sect. He adored his parents, loved his mosque, and was proud of his Islamic community. His family was Muslim-American, his father a Navy officer. Nabeel spent much of his childhood in Scotland, where his father served at a naval base, before relocating to the US. Like most Muslims, he believed Muhammad self-evidently superior to the Prophet Issa (Jesus, whom he nevertheless revered), and the Quran (preserved without error) much nobler than the corrupted Christian Bible. Islamic culture, of course, was obviously the most perfect in the world.
The Ahmadis are evangelical Muslims, and Nabeel's parents encouraged him to talk about religion with his friends. This is how he made friends with a young man named David Wood at Old Dominion University. David was a recent Christian convert, and the two young men spent hours and hours discussing the differences between their two faiths. Their strong friendship and trust in one another allowed them to remain close in spite of their arguments. David was in a position to call on some pretty heavyweight Christian apologists (like Gary Habermas) to support him. Nabeel was surprised – and disappointed – to find that his Muslim mentors could not summon compelling arguments to defend the Prophet or his book – Islam came down, in the end, to bald appeals to authority.
The story of Nabeel's struggles with the idea of leaving Islam is heartbreaking. It meant not only abandoning his very concept of himself, but it meant hurting his parents, who were extremely fine and loving people. It says much about them that they have managed to maintain a relationship with him, even an affectionate one, since his apostasy.
This edition includes several appendices, in which the author and other contributors go more deeply into the arguments and evidence that Nabeel worked his way through on his personal pilgrimage. This material will not only help Christian readers understand their Muslim neighbors better, but it will impress them with the level of rational evidence supporting the Christian narrative (especially when compared with claims for Islam and the Quran, which have generally been left alone by critical scholars until recently).
The element of dreams and visions, which forms a large part of the story, will be a challenge for some Christians. But I understand it to be a not uncommon phenomenon in Muslim conversions, and I'm not going to criticize it.
Seeking Allah, Finding Jesus is a highly impressive autobiography and apologetic work. Most highly recommended.


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The Right Rehabilitation Treatment Center: Find Yours
When we know all the consequences of addiction, from despair and hopelessness, to more tangible issues like the millions in healthcare it costs tax payers and the crime that arises from it, why, then, is it so difficult to find effective rehabilitation for people who are lost in their drug and alcohol use? A process that should be entirely devoted to healing and recovery is instead riddled with obstacles and confusion. But not anymore. One call to us at our toll-free number will put you in touch with a sensitive and compassionate placement counselor who can match you with the right treatment facility; or, if it suits you better, you can fill out a quick form on our website and receive a timely callback. What could be a greater gift for you or for someone you love who is struggling with addiction, than to put yourself in touch with a national organization where the sole aim is to quickly help those suffering with drug or alcohol abuse.
Get It Right the First Time
The most important factor when seeking a rehabilitation center is to find out its rate of success. But that depends largely on how suitable the program is for each individual seeking help. Therefore, it's important not only to get it right, but to get it right the first time. Life, though a blessing, is fleeting, and oftentimes, when drugs or alcohol are involved, it can be cut too short, too soon. That's why it's so important for the one with the addiction, or the concerned family member or friend in their life, to reach out.
The Most Important Phone Call You Can Make
Yet just an initial search for the right program can be overwhelming in the extreme. There are literally thousands of treatment facilities all over the country, and with time as sensitive as it is, you can't spare an extra second sifting through hundreds of websites or brochures. That's why this phone call could be one of the most important ΓÇô and reassuring ΓÇô you'll ever make. With so many options ΓÇô drug-specific, culture or religious-specific, prices to consider, locations ΓÇô you might feel as though you're trapped in an endless maze. We can show you how to get out. Our placement specially trained counselors, who are experienced and sympathetic to your needs can ascertain, based on your specific needs, the best possible treatment facility for you or your loved one. You deserve a rehab center that makes you feel understood from the very start. The best part is that no matter where you live or what you can afford, you will be directed toward a treatment center with a reputation for effectiveness.
The sad fact of addiction is that it keeps a powerful grip on those who do nothing to stop themselves from using or drinking. While it would be wonderful to be able to close your eyes, pick a name out of a hat and find the rehabilitation center that will get you off drugs or alcohol that's now how it works. What does work is calling us and speaking to one of our counselors. One call and you will be on your way not only toward finding the right treatment center for you, but to an addiction-free life.


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[one_half]Kelly Marshall, designer and weaver, creates textiles for residential and commercial settings. Using the Scandinavian rep weave technique, she intricately blends color with complex pattern to make inviting textiles that add warmth and familiarity to public interiors.
Marshall brings twenty-two years of experience collaborating with designers, art consultants, and architects. For each project, she pulls together elements of the existing interior design, and facilitates the creative process from vision to completion. These exquisitely textured weavings are made of non allergenic cotton and linen fibers. Her textiles enrich the environment in hospitals, corporations, restaurants, country clubs, banks, museums, libraries, and universities nationwide.


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Rio Grande Scenic Railroad
The Rio Grande Scenic Railroad excursion train rides take you through breathtaking mountain valleys and passes on miles and mile of historic trails. The steam and diesel trains transport you to charming and historic western towns from the heart of the San Luis Valley.
Trains depart from Alamosa to the scenic mountain town of La Veta, or ride the Valley Steam Flyer to Monte Vista or the Cumbres Connection to Antonito. Access to the Roots and Boots Music Festival is available from Alamosa or La Veta. Tickets may be purchased online or by calling 1-877-726-RAIL. Regular season runs Memorial Day Weekend through the end of October. View the full 2012 calendar for special events and themed trains.


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10 Big Steam Room Benefits. Part III
Advantage #8 – You Meet Individuals
People are crowd creatures and those that are constantly alone don't generally do as well. Having companions is essential for psychological wellness and basically, they can be genuinely amusing to have. Well setting off to a steam room a couple times each week is an awesome approach to mingle, meet new individuals, and possibly make some long lasting companions. Setting off to a steam room doesn't just make you more advantageous, yet it likewise expands your social association and bliss as well.
Advantage #9 – Helps With Muscle Development And Repair
Another tremendous advantage that accompanies utilizing a steam room all the time, particularly after a workout, is on account of they help in the muscle recuperation and the development procedure. Put in basic terms, steam rooms can recuperate your muscles and make them become bigger as well. On the off chance that you are into working out and lifting weights, sitting down for a steam after each workout is an extraordinary compliment to your standard schedule.
There are really two unique reasons in the matter of why muscle development and repair is prodded on by the warmth of a steam room. One of these reasons is that a steam room causes the body to discharge HGH or human development hormone. Human development hormone in the body causes the muscles to develop and repair at an expanded rate.
The same can be said for heat shock proteins, another compound which is discharged when the body is presented to high temperatures for a drawn out timeframe. Both of these substances assume their part in helping your muscles to mend faster and develop greater, something that is critical in the event that you practice consistently.
Advantage #10 – Unwinding After Anxiety
While we are on the theme of muscle recuperation, your muscles need time to rest and recover after a strenuous workout schedule. Additionally your muscles need to chill off satisfactorily and they should be stretched out after each activity schedule. Not giving them a chance to chill off legitimately and not stretching may bring about extreme harm.
Being in a steam room is not cool per say, but rather it counts as a cool down schedule. Since being in a steam room includes working your heart at a somewhat higher level, it's an awesome approach to move from a strenuous workout to a not at all that strenuous cool down.
Besides the warmth in the steam room causes your muscles to unwind and relax, something that likewise helps in the recuperation procedure. As it were, utilizing a steam room after each workout can really expand your athletic execution.
Steam Room Benefits: The Conclusion
On the off chance that you have never taken a stab at utilizing a steam room, you may very well need to give it a shot. You will be astounded in the matter of how great it can make you feel. In addition you will be amazed in terms of how much better your brain and physical capacity is from something as straightforward as sitting in a steamy space for a couple of minutes for every day.
Loose muscles, a sound personality, a superior working heart, an great lungs are only a few advantages to be procured from a steam shower, in addition to numerous others. In the event that you have any inquiries or remarks for us, please let us know and we will do our best to answer them. In the event that you are truly into working out or simply need to keep your body and brain sound, we would prescribe taking a steam a couple times each week.


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We'll be running daily BATT's all Thanksgiving week.
An excellent development from MIT:
For many people, it has become routine to go online to check out a map before traveling to a new place. But for blind people, Google maps and other visual mapping applications are of little use. Now, a unique device developed at MIT could give the visually impaired the same kind of benefit that sighted people get from online maps.
The BlindAid system, developed in MIT's Touch Lab, allows blind people to "feel†their way around a virtual model of a room or building, familiarizing themselves with it before going there.
Once [Touch Lab director Mandayam] Srinivasan obtains additional funding, he…believes BlindAid could be used to help blind people not only preview public spaces such as train stations, but also plan and travel by public transportation using virtual route maps that they can download and interact with through touch.
Empowering the visually impaired by enabling them to "preview" an unfamiliar place by sense of touch is just the beginning. The integration of GPS technology with the ubiquitous (and increasingly detailed) mapping of the world available online opens up huge possibilities for the blind, requiring only that the data be made available through a non-visual interface. As attention begins to turn to the mapping of interior spaces, the utility of such information grows exponentially.
One day soon, blindness will be a thing of the past. In the mean time, it is encouraging to see how emerging technologies (and the resulting emerging possibilities) continue to chip away at the barriers the visually impaired have always encountered when trying to interact with a world that assumes vision.
Live to see it!


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Isis Wings
Wings of Isis are a dramatic belly dance tool for capturing and holding the attention of an audience. In the hand (or more correctly, on the arms) of a skilled and experienced dancer, Isis wings elevate the performance, making the dancer's subtle movements more dramatic and visible to the audience. We can make Isis Wings in any color, size, quantity you want and for best price.


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On the eve of Emmy voting starting up on Monday, Amazon will make sure that voters get its FYC message by delivering it in person on Sunday.
That's when Amazon's reps will canvass greater Los Angeles to hand out a comprehensive voters' guide to its competing programs. "Physical copies will be delivered to eight different areas, including Beverly Hills, West Hollywood, Burbank and Culver City by brand ambassadors," says a rep. "At each stop we anticipate that we would hit about 500 homes and 500 local businesses."
A digital copy is also available to Emmy voters at ConsiderAmazon.com.
The 29-page voters' guide is full of big glossy photos and comprehensive listings of who's competing in each category, including casting, costumes and production design plus the top slots for Best Comedy and Drama Series. Shrewdly, it reminds voters of past kudos success like "Transparent" winning Emmys for Best Comedy Actor (Jeffrey Tambor) and Directing (Jill Soloway) over the past two years and "Goliath" snagging the recent Golden Globe for Best Drama Actor (Billy Bob Thornton). Equal oomph is given to Amazon's victories and nominations at BAFTA, Critics' Choice Awards and the Peabodys.
Also scattered throughout are hosannah quotes from TV Guide, Variety and other major media about comedies "I Love Dick," "Catastrophe," "Mozart in the Jungle," "Fleabag," "One Mississippi," "Red Oaks" and dramas "Bosch," "Man in the High Castle," "Sneaky Pete" and "Z: The Beginning of Everything."
Zip codes to be covered:
Beverly Hills (90210 – 90212)
Homes and apartments on blocks in between Wilshire and Olympic from Doheny to Roxbury.
Local Shops: Starbucks on Little Santa Monica Blvd., Century City Mall (just outside zip), Coffee Bean, Pete's Coffee and hotels like the Peninsula and Four Seasons.
West Hollywood, Miracle Mile (90046, 90069, 90036)
Homes and apartments on blocks in between Sunset Blvd and Melrose Ave. from La Cienenga to La Brea and blocks between Wilshire and Beverly Blvd. from Fairfax Ave. to Highland Ave.
Local Shops: Alfred's Coffee, Verve Coffee, The Assembly, Longshot Coffee, Dialog Cafe, Black Bicycle Cafe, Smith and Tait, Coffee Commissary, Coffee Coffee, Starbucks Reserve Roastery and Coffee Bean.
Studio City (91604)
Homes and apartments between Coldwater Canyon and Laurel Canyon and in between Ventura Blvd. and Riverside Blvd. Blocks in between Laurel Canyon Blvd. and Vineland Ave. and in between Magnolia Blvd. and Moorpark St.
Local Shops: Comoncy, Crave Cafe, Coffee Fix, Belwood Bakery, Aroma Coffee and Tea Co., Vivian's Millennium Cafe.
Silver Lake, Echo Park, Los Feliz (90026, 90027)
Homes and apartments between Virgil and Glendale Blvd. and Beverly Blvd. /Silver Lake Blvd., in between Sunset Blvd. and Temple St. Blocks between Hyperion Ave. and Silver Lake Blvd between sunset Blvd and Rowena Ave/Glendale Blvd. Blocks between Alvarado St. and Echo Park Ave. between Sunset Blvd. and Stadium Way. Blocks between Loz Feliz Road and Fountain Ave. in between Hillhurst Ave. and Western Ave.
Local Shops: Lamill Coffee Boutique, Intelligentsia Coffee, Dinosaur Coffee, Silverlake Coffee, Cafeito Organico, Caffe Vita, Blue Bottle Coffee, Woodcat Coffee Bar, Winsome, H Coffee House, Bru Coffee Bar
Toluca Lake (91602)
Homes and apartments between Cahuenga Blvd. and N. Hollywood Way, and between Riverside Dr. and W. Verdugo Ave. Blocks between Cahuenga Blvd. and N. Hollywood Way, and between Magnolia Blvd. and W. Verdugo Ave.
Local Shops: Aeirloom Bakery, Coffee Bean, Simply Coffee and Boutique, Moby's coffee and tea co., Republic of Pie, Joe Coffee, Coffee Commissary.
Burbank (90068)
Homes and apartments between W. Burbank Blvd. and W. Magnolia Blvd., and between N. Buena Vista St. and Victory Blvd. Blocks between E. Kenneth Rd. and S. Glenoaks Blvd. between E. Olive Ave. and Grandview Ave.
Local Shops: Basecamp, Romancing the Bean Cafe, Blvd Cafecito.