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Enamel Cancer Ribbon PinThis Cancer pins can be a gifts ,To a friend or family menber that were just diagnosed with Cervical Cancer .As a cancer sufferer,it will bring you courage and belive. that will be a really appreciate anything that will help research in beating this disease expecially if you recently had surgery .
When you have someone you know and love go through this horrible disease, it's so hard to help them because the pain they are going through is something you can only help so much. By wearing the pin, it shows my support not only for my person but for every cancer patient out there. It helps spread awareness and it shows that we are part of their fight. We may not be able to wish away their pain but we are there to hold their hand, be by their side, and fight this horrible disease till the end with love and support.
what is more , It can make more people aware of this deadly, disfiguring Cancer.It would most certainly way to spread awareness to family and friends and a small reminder that we should protect ourself and keep a heath body.
To those who lost their family who were unluckly to got cancer , wear this pin bought with much pride and a heavy heart. No one fights alone!!!
Makes you more proud to work in your profession and caring for patients with liver cancer.
Once touched by cancer, it never goes away. This one little pin is recognized universally and encourages the opening to a conversation. May all survivors and supporters continue to carry the message!!
We can understand how important it is to express your support when someone you care about has cancer. We offer meaningful and inspiring badges in various colors of cancer awareness. Whether it's breast cancer, lung cancer or prostate cancer, we can help make a difference and customize according to your require. Browse our cancer awareness products , find perfect gifts for loved ones, commemorate the dead or celebrate a survivor, even yourself.
Appendix Cancer - Amber
Bladder Cancer - Marigold / Blue / Purple
Brain Cancer - Grey
Breast Cancer - Pink
Carcinoid Cancer - Zebra Stripe
Cervical Cancer - Teal / White
Childhood Cancer - Gold
Colon Cancer - Dark Blue
Esophageal Cancer - Periwinkle
Gallbladder / Bile Duct Cancer - Kelly Green
Head and Neck Cancer - Burgundy / Ivory
Hodgkin's Lymphoma - Violet
Kidney Cancer - Orange
Leiomyosarcoma - Purple
Leukemia - Orange
Liver Cancer - Emerald Green
Lung Cancer - White
Lymphoma - Lime Green
Melanoma - Black
Multiple Myeloma - Burgundy
Ovarian Cancer - Teal
Pancreatic Cancer - Purple
Prostate Cancer - Light Blue
Sarcoma / Bone Cancer - Yellow
Stomach Cancer - Periwinkle
Testicular Cancer - Orchid
Thyroid Cancer - Teal / Pink / Blue
Uterine Cancer - Peach
Cancer Caregiver Gifts - Plum
Honors Caregivers - Plum
Latest News
- What else can we do with your logo2019-12-05
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- Function of Lapel Pin2019-10-11
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Contact Us
Contact: Cora Chen
Tel: +86 17783868684
Add: DongShen Town,Zhongshan City,Guangdong Province,China


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You and your students can add your names and become signers of the Constitution!
Get Ready for Constitution Day!
We have programs and resources to help you teach about the Constitution on Constitution Day or any day!
Communication in History: Resources for NHD 2021
Find primary sources and teaching activities for National History Day!
Commemorating the 19th Amendment
Join us for webinars, online student programs, and more to commemorate the centennial of the 19th Amendment.
New Mini-Webinar Series: DocsTeach for Virtual Learning
Will you be teaching online this fall? Join us this August for our mini-webinar series: DocsTeach for Virtual Learning!
Summer & Fall Online Student Programs and Professional Development Webinars for Educators
Join us online this summer and fall! We have programs for K-12 students and professional development for educators.
European Refugees in the United States During World War II
A new teaching activity focuses on a teenage refugee's written composition about his experience in the United States during WWII.
Teaching the Vietnam War with DocsTeach
DocsTeach, our online tool for teaching with documents, is full of primary sources and tools for teaching about the Vietnam War.
New DocsTeach Mini-Webinars
Getting Started with DocsTeach Mini-Webinars are open to teachers and parents of students in all grade levels. Each 20-minute session will highlight a different aspect of DocsTeach.
Cultural Diplomacy Following World War II
After World War II, the United States fostered cultural exchange in the interest of diplomacy. We have a number of online learning activities to explore this time period.

subset: commoncrawl


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Henry James Hall
From Ballarat and District Industrial Heritage Project
Henry James Hall was an artist whose premises (according to the Australasian Federal Directory) were located on Eyre Street, Ballarat West. [1] He worked at the Ballarat School of Mines.
In 1908 Henry Hall was an artist with an Art Studio called 'Ferndale' at 25 Eyre Street, Ballarat.
- The death occurred at his residence, Doveton Street north, on Saturday, of Mr Henry James Hall, the well known drawing instructor, at the age of 70 years. The deceased had been ailing for a very long time, and his death was not unexpected. The late Mr Hall was born in London in 1846. He was educated at Dr Brookleck's school, and was South Kensington Art School, and was a chorister in St Paul's Cathedral, London. Mr Hall was engaged for seven years as a portrait painter with the late Thomas Fossey and was also portrait and landscape painted at Maidstone, Kent, for about 11 years. After coming to Ballarat he joined the Ballarat East Art School as mechanical, architectural, and drawing instructor. In 1885 he was appointed instructor of drawing and painting and building construction at the Ballarat School of Mines. He was Worshipful Master of the Orion Masonic Lodge in 1893, and later received appointment as P.S.G.D. of the Grand Lodge of Victoria. He was also P.C. Ranger of the old A.O.F., and was P. Arch of the U.A.O.D. at Maidstone, Kent, as well as being an ex-sergeant of the Royal West, Kent. The deceased leaves a widow, two sons and three daughters. The funeral will take place today at 2 o'clock to the Ballarat Old Cemetery.[2]
- Robert Lewis, aged twenty-two, who said he was a member of the Masonic brother-hood in Western Australia, was charged at the Ballarat East court on Tuesday with stealing Masonic regalia and a jewel valued at £12, belonging to Stephen Mason, insurance agent, of Melbourne, where he is secretary of the Naval and Military lodge. Prisoner was also charged with stealing Masonic regalia and a jewel valued at £10 belonging to Henry J. Hall, artist, of Ballarat. The alleged offences were, as reported in "The Age," committed in April last while Lewis, who is a laborer, was on fraternal visits to MasoniC lodges of Ballarat. Accused pleaded guilty, and was sentenced to six months' imprisonment on each charge.[3]
- ...An ex-President's certificate [of the Mining Managers' Association Ballarat Branch, handsomely embellished with a picture of a mining scene by Mr Henry J. Hall, was presented to Sir Phil Lewis on behalf of the members. Mr R. Ditchburn made the presentation in an appropriate speech, and was supported by several speakers, who eulogised the ex-president for his capabilities as their chief officer and his merits as a citizen. Mr Lewis having replied, a vote of thanks to the chairman closed the proceedings.[4]
See also
Henry Hall, son
- ↑ Rogers, J. W. F. (ed.). (c. 1887). The Australasian Federal Directory of Commerce, Trades & Professions. Melbourne: J. W. F. Rogers.
- ↑ Ballarat Star, 21 May 1917.
- ↑ The Age, 20 July 1904.
- ↑ Ballarat Star, 28 January 1907.
Further Reading
External links
--Beth Kicinski 10:12, 19 December 2011 (EST); --Clare K.Gervasoni 18:33, 4 January 2015 (EST); --Clare K.Gervasoni 22:47, 16 April 2017 (AEST); --Clare K.Gervasoni 23:28, 28 March 2019 (AEDT)


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Color Screen Gameboy iPhone Case
— Regular price USD $39.90 Sale price USD $25.90
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— Regular price USD $39.90 Sale price USD $25.90
Color BLACK
Brand APPLE
Phone model iphone 6/7/8
You can now protect your phone in style while you show off your love for gaming gear at the same time. This slim case, which snaps onto the back of your iPhone, comes loaded with games and has a familiar control layout. It comes with 36 pre-loaded games and relive those childhood memories!
It does not interfere with the normal function of your phone and also gives access for your phone's buttons, microphone, speaker, headphone jack, dock, and flash. It comes with fast USB charging with up to 6 hours of play time on a full charge. Perfect for long trips, commutes, or just to have fun.
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Ladybug Long Wallet
The Picard Ladybug Long Wallet adds a sophisticated touch to your wardrobe. Features a zip down opening, multiple card slots, 1 back zipped pocket and also comes with an internal zipped compartment to organise your bills, cards and coins.
- Material: Leather
- Zip down opening
- Multiple card slots
- Internal zipped compartment with card slots
- 1 back zipped pocket
- Height: 11 cm
- Length: 21 cm
- Width: 2 cm
Measurement Guide
For bags' drop length:
Drop length pertains to the distance of the top of the bag to the resting point of the strap against your shoulder.
For belts:
Belt width corresponds to the width of the buckle hole. The belt body will have a 2mm deviation to prevent friction against the buckle.
Belt length corresponds to the measurement of length without the buckle.


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From now on, the pension supplement that in Spain has only been granted to mothers with an occupational disability pension and two or more children, is also awarded to fathers in a comparable situation. That is what the European Court decided on Thursday.
A father of two daughters was awarded a 100 percent disability pension by the Spanish social security institute INSS. The man appealed against this because a mother in the same situation receives 5 percent extra under Spanish law. The father wanted to receive the same arrangement, but was not approved by the INSS.
On appeal to the labor court, who went to the Court of Justice of the European Union, the man was still right. The Court finds that the Spanish law is against the equal treatment of women and men in the field of social security. Fathers with at least two biological or adopted children are discriminated against based on their gender, which is prohibited.
The Spanish law was aimed at compensating women because they often build up a lower pension than men. This is especially true if they have interrupted their career one or more times due to parenthood.
The Court now judges that Spanish law does not mention these circumstances, but only makes a distinction based on gender. Men who interrupt their career because of parenthood cannot claim a benefit, while women who continue to work can make use of it. According to the Court, that makes the law discriminatory.


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Current Event June 16, 2014
Politics Civics/Government Journalism
It has been 40 years since the publication of "All the President's Men" by Washington Post reporters, Bob Woodward and Carl Bernstein. The popular book was made into a movie at the same time. The authors of the book recently reflected on their reporting that revealed President Richard Nixon was trying to rig his re-election campaign. Listen to this radio story to teach your students about Watergate and its place in history.Read More
Current Event May 15, 2014
Civics/Government Technology Journalism
Drones are not just for military use anymore. They are being used by journalists to report stories. But this is raising some privacy concerns.Read More
Current Event November 25, 2013
US History II Journalism Storytelling
Decades of Americans are able to remember where they were at the moment they heard President John F. Kennedy had been shot and killed in Dallas, Texas on November 22, 1963. Fifty years later in this radio story we relive the events of that fateful day through the memories of two reporters who were there. Hugh Aynesworth was a local reporter for The Dallas Morning News and Sid Davis was a White House correspondent traveling with the president's press corps. Put yourselves in their shoes as they take you through how they learned about and covered the assassination.Read More


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Unfractioned Heparin and Low Molecular Weight Heparins
Pharmacology March 28, 2011
Unfractioned Heparin- Unfractioned Heparin- is derived from porcine intestinal mucosa or bovine lung tissue. UFH catalyzises that inactivation of thrombin and factor Xa by inhibiting Anti-thrombin III. At usual dose it prolongs TT and aPTT and has a minimal effect on PT/INR. Benefits of ...Read More


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Hydrilla Verticillata Control Removal in Callahan California
Hydrilla Verticillata in Callahan, CA can be a real problem for municipal and home owners ponds and lakes as well as golf course ponds throughout the State of California. Now there is help with controlling and removing Hydrilla Verticillata in Callahan. View our equipment at dkenvironmental.com.
Aquatic plants are plants that have adapted to living in marine places (salt water and / or freshwater). They're also categorised as hydrophytes and / or macrophytes. These kinds of plants require specific variations for existing submerged in water, or at the water's surface. The most common variation is aerenchyma, but floating leaves and very finely dissected leaves are also prevalent. Aquatic plants are only able to flourish in water or in soil that's entirely saturated with water. They are subsequently a common a natural part of wetlands.
Aquatic plants are by and large a beneficial portion of the water body, whether it's a lagoon or perhaps a fish-pond. The water vegetation is a source of food, refuge and oxygen to the creatures currently in water-feature or lake. Then again remaining uncontrolled these water plants could possibly spread rapidly and constrain the activities in the fish pond or lagoon. That's when these types of aquatic plants turn into water weeds.
A simple description of a water weed is a plant that grows (usually too densely) inside of an area in a way that it prevents the usefulness as well as enjoyment of the particular area. Several prevalent examples of water plants which can turn into unwanted weeds are water milfoil, duck weed, pondweed, hydrilla, water hyacinth, cattail, bulrush, ludwigia, and numerous others. They may flourish throughout fish ponds, lakes, streams, canals, navigation channels, storm water basins and channels, wetlands and lagoons. Typically the growth may perhaps be due to a variety of components for instance excess nutrients in the water or even the arrival of rapidly-growing exotic varieties. The down sides caused by aquatic undesirable weeds are numerous, ranging from unpleasant growth and nuisance aromas to blocking of waterways, flood damage, fishing boat damage, as well as drowning and impairment of water quality.
In most instances it is more efficient plus affordable to employ an expert water weed control business to remove and control your aquatic weed problems. For California probably the most competent company is DK Environmental. DK Environmental can be found in the San Francisco Bay area yet executes aquatic weed eradication throughout the State of California. The machines that DK Environmental utilizes is quite distinctive to the western U . S. Featuring number of DK can access virtually any water system.
Get rid of Hydrilla Verticillata in Callahan. It is easy to make contact with Dave McNabb @ DK Environmental right away at 925-935-4200


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Mail Purchase Brides from Brazil South Usa Brides On Line Catalog The planet Cup in 2014 place Brazil securely in the map along with not only for legislation soccer! Observers may well not fail to take notice of the house developed ability composed of the beautiful Brazilian girls supporting, looking at and additionally cheerleading. Mail
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← Back to Case Studies
Case Study: Power Plant, Puerto Rico
Riding the storm – how a Sylmasta contaminated water pipe repair helped keep power going in Puerto Rico during Hurricane Maria
When a contaminated water pipe in a Puerto Rican Power Plant began leaking in 2015, the Power Authority had two choices – find a way to carry out a repair without needing to take the pipe out of service or shutdown the generator it was connected to.
Thanks to Sylmasta, a live leak repair was possible. Which was just as well as within 18 months, Puerto Rico would need all the power capability it could muster after the most devastating natural disaster in the island's recorded history.
The pipe in question was responsible for running contaminated water back to a treatment plant. At some point, a small crack had appeared in the bottom of the pipe which was now leaking water.
Nobody was quite sure how the damage had occurred, but equipment which had been stored under the pipe had recently been moved and may have inadvertently impacted on the pipework.
To carry out a repair with the pressure turned off or to completely remove and replace the damaged part, the generator that the pipe was connected to would have needed to be shutdown. This exercise would have been expensive and reduced the Plant's capacity for generating power.
There was also a danger that once taken out of service, the repair could have taken a significant amount of time owing to how long it would take for new parts to be both delivered and fitted – or it may not have been completed at all.
Instead, the Power Authority turned to Sylmasta to supply a contaminated water pipe repair solution. Firstly, Wrap & Seal Pipe Burst Tape was applied to the pipe to seal the leak. Wrap & Seal stretches by 300% and is twice the thickness of any other self-fusing pipe repair tape, ensuring that it fixes leaking pipes even when pressure cannot be turned off.
Wrap & Seal was then overwrapped with SylWrap Pipe Repair Bandage, which sets rock-hard to form a protective layer over the Pipe Repair Tape, providing a permanent repair.
The repair was carried out inside of 30 minutes at very little cost to the Power Authority. The true value of fixing the leaking contaminated water pipe though only became apparent in 2017 when Hurricane Maria hit Puerto Rico, Dominica and the U.S. Virgin Islands.
Hurricane Maria was the deadliest Atlantic Hurricane for nine years, a category five storm which ripped across the Caribbean. Central to the relief efforts both during and after Maria was keeping power going in Puerto Rico, something which the Sylmasta repair helped to do.
Six months after Hurricane Maria, the contractor who had carried out the repair got in contact. He said that without the Sylmasta repair, then the Power Plant would have had one less working generator at a time when Puerto Rico needed all the power available to it.
As a result, the Power Authority were extremely glad that such a quick and easy repair had been available to them.
Products used
Both of these products are available in the SylWrap Universal Pipe Repair Kit and the SylWrap Pipe Repair Contractor Case which contains enough equipment to carry out multiple fixes.
Repair Photos
If you have an application you would like to enquire about, then please get in touch
Call: +44 (0)1444 831 459
Email: firstname.lastname@example.com


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Contact Info
Cr Quality Painting
33734 N State Rd
Tel: 815-784-3258
Update this listing
About Cr Quality Painting
Cr Quality Painting are professional Painting Contractors located at 33734 N State Rd, in the Illinois city of Genoa. Cr Quality Painting can be contacted on 815-784-3258.
Location Map Report an error
About this listing on ICC
provided the information about Cr Quality Painting that you see on this listing. If you are aware of any new information about Cr Quality Painting please fill out the update form with as much detail as possible.
If you would like to claim your business, add special offers, logos and photos, click here to find out how to claim and enhance your listing.


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Fresh masseuse has first time with her lesbian boss Mindi Mink6 minadult video
Liv Revamped What a pair. Mindi was probably in heaven. That cinnamon beautys pussy probably tasted like hot butterscotch.What is the name of the curly hair girl
We've got our closets stocked with denim miniskirts and plenty of cutout, open-back tops that draw all eyes to — you guessed it — our booties. And when we're wearing our high-waisted, flared jeans, we can't help but want to spin around and show off our backsides because, hey, they look fine. But that doesn't mean we're constructing our outfits without sophistication in mind. The 23 stylish outfit ideas here will help you play up and emphasize your booty in a way that feels elevated and on-trend this season. Scroll for unique ways to show 'em what your mama gave you — but in a subtly sexy sort of way. View On One Page.


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About cache blend node
This node would always cache the input pose of last frame, and blend to new input pose when
ToggleFlag is changed.
Why do we need this node?
If you are working on a real commercial UE4 project, you may want to reuse anim graph structure by changing playable assets of the anim nodes(eg. BlendSpace, Anim Sequence, Evaluator, and etc. ) during runtime:
But here comes the problem:
Since those variables are changed in one single frame. Animation pose would change suddenly, thus we cannot get a nice transition:
This problem needs to be solved!
Development issues of this node
Random crash after caching input pose
In the very beginning, I use a
FCompactPose class member to store input pose in the end of
Evaluate_AnyThread function like this:
But the engine keeps crashing randomly — sometimes in render system, sometimes in slate viewer. It seems that the memory is broken.
After digging into
FCompactPose structure, it seems that
FCompactPose is allocated with a stack mem marker:
struct ENGINE_API FCompactPose : public FBaseCompactPose<FAnimStackAllocator>
Thus it is fine to create a
FCompactPose inside an evaluation function. But it is not okay to make it a class member.
As a result, I use
TArray<FTransform> to cache input pose. A
FCompactPose would be created from this array during
Evaluate_AnyThread function. Then we can use
FAnimationRuntime::BlendPosesTogether to perform blend.
Issues about
Since UE4 have already got its own blend pose function, it might be better to use it (Fine, I am simply much too lazy to write another function).
FAnimationRuntime::BlendPosesTogether accepts a pose array, a curve array and a weight array to give a valid pose and animation curves:
void FAnimationRuntime::BlendPosesTogether(
And we need make sure that you have the input pose the first element. And here is why:
BlendCurves function, the output curve would firstly
initfrom the first curve element:
void InitFrom(const FBaseBlendedCurve<OtherAllocator>& InCurveToInitFrom)
UIDToArrayIndexLUT is a
TArray<uint16> const * pointer, thus this function performs a shallow copy.
Thus we cannot make our newly-created the first element, otherwise a pointer error would occur and drives you mad.
Yet another way
There is yet another way to solve this problem. We can directly modify
AssetPlayer Node to perform cross-fade between old asset and new asset when the asset has been changed. In short, cache old asset value, and blend between old&new asset with the same time accumulator.
Method comparison
Multiple Transition
Cache Pose can handle multiple transition since we always blend from current pose to target pose — No matter what the target pose is.
Cache Asset cannot handle multiple transition, unless you store multiple asset, and evaluate&blend between them, which cause performance issue.
Cache Pose surely has better performance, since we do not need to evaluate old assets.
Cache Pose has better maintainability, since it has been decoupled with any asset player node, whereas
Cache Asset requires modification to official animation node.
Cache Pose can be placed anywhere, but
Cache Asset can only works with asset player node.
Animation Detail
Cache Asset can provide better animation detail, since both old and new animation are still running. But
Cache Pose can only provide a single pose, which lacks some detail.


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Contract Law > Discharge
Previous: Contractual terms
The discharge of a contract means that it is bought to an end. For most contacts, this is done by both parties fulfilling their obligations. However, a contract may also be discharged in other ways. Where there is a common mistake, a contract is never made, and where a contract is frustrated or breached in a repudiatory manner, it may be discharged prematurely.
Common mistake
Where parties to a contract are both mistaken in some way before the contract is concluded, the contract may be void, that is it is treated as if it never existed. This is different to frustration, which can only occur after conclusion.
The case of Bell & Lever Bros [1932] is a good illustration of how the doctrine of common mistake operates. As a brief background, Bell and another person named Snelling were employed by Lever Bros to run and make profitable a company. They successfully did this, and once Lever Bros was satisfied that their objectives had been completed, both Bell and Snelling were made redundant with huge payoffs to say thank you. However, shortly after paying this money, Lever Bros discovered that prior to the redundancy contracts being finalised, Bell and Snelling had both engaged in some personal trading, which had been expressly prohibited by their employment contracts. If Lever Bros had known this before, Bell and Snelling could have dismissed without any payoff. They therefore sought to recover the payoff sums...
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Emperor Norton's Fantastic SF Time Machine Walking Tour Reviews & Ratings
Very interesting tales of San Francisco told by a true area native!reviewed Feb 16 2013 report as inappropriate
Though I am a native, I cannot believe how many cool things about SF I learned on this tour! We had an amazing time and would recommend this to anybody of any age. There are 20 highly interesting stops and the guide is funny, personable,...continuedreviewed Aug 18 2012 report as inappropriate
A fun, interesting and informative tour. A beautiful day to walk the streets of San Francisco with one of The City's most colorful characters. Perhaps some of favorite moments was seeing how others reacted to the Emperor, awe, delight and...continuedreviewed Sep 27 2012 report as inappropriate
He is a great storyteller and very articulated with the historical information. Awesome... so is SF!reviewed Dec 20 2012 report as inappropriate
Fun and interesting! Like the more unique, strange, historical and beautiful gems we discovered.reviewed Feb 14 2013 report as inappropriate
Very entertaining 2 hours and 30 minutes with an engaging and informative tour master.reviewed Jun 20 2015 report as inappropriate
A different way to see San Francisco, with a knowledgeable tour guide in character as one of the city's most famous eccentrics. Our tour lasted nearly three hours, so be prepared and wear comfortable walking shoes and bring layers (to combat the...continuedreviewed Sep 05 2015 report as inappropriate
Fantastic! I've lived in the Bay Area for 6 years and am leaving for good in a few weeks (tears will be shed). Decided to take this tour for kicks with my best friend, and it blew out minds. Best decision we made in a long time. 3 hour tour,...continuedreviewed Apr 18 2015 report as inappropriate
Very nice, interesting, well informed, engaging guide, learned some new things about a city I've visited many times and saw things I never would have seen on my own. Definitely worth the time & money.reviewed Sep 01 2012 report as inappropriate
So much information, learned a lot about the Union Square and surrounding area. Have spent much time there over the years walking by buildings not knowing their history. Highly recommend for someone who has the time ( 3 hrs.) and wants to learn...continuedreviewed Nov 13 2014 report as inappropriate
The tour was really interesting. The guide had all is facts and presentation was great. He welcomed any comments & took them in stride.reviewed Jul 27 2013 report as inappropriate
We had a great time! This was an awesome tour! Loved learning all about San Francisco from the very talented Emperor Norton himself! Would highly recommend this tour! First thing we did when we arrived in San Fran. Keep up the good work...continuedreviewed Dec 26 2015 report as inappropriate
Great experience. Very informative and entertaining.reviewed Feb 21 2015 report as inappropriate
More suitable for a family with youngish children. Also should mention in description that it is not a loop so you get left off far from where you started. Visitors may find themselves in a bit of difficulty to find their way vackreviewed Jan 05 2017 report as inappropriate
As a local, I have participated in a lot of tours in and around San Francisco. Hands down, Emperor Norton's is one of the BEST!reviewed Mar 09 2013 report as inappropriate
Emperor Norton tour of the history of San Francisco was informative & fun. Emperor brought us to various areas where we would never have gone if not for the tour - & we live in San Francisco!reviewed Jul 27 2017 report as inappropriate
Excellent tour. The emperor is knowledgable, conversational and a delightful guide to San Francisco. You will learn about SF history, architecture, crime and other topicsreviewed May 15 2014 report as inappropriate
Excellent tour. I am local and Iearned a lot. The Emperor was fun and informative!!reviewed Nov 09 2019 report as inappropriate
Great tour with lots of quirky San Francisco information presented with humor and accurate research! Thanks!reviewed Oct 25 2012 report as inappropriate
I've lived in the Bay Area my entire life, decided to play tourist and had a blast. Definitely learned a bit of history not taught in school.reviewed Jun 27 2015 report as inappropriate


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President Donald Trump and First Lady Melania touch down at Stansted Airport
American president Donald Trump touched down at Stansted Airport, along with nine other international heads of state, for this week's NATO summit in Herts.
The 73-year-old flew straight into the kind of controversy which has become par for the course in the UK on his two previous visits.
This time he arrived after dark, landing in Air Force One, a highly-customised Boeing VC-25 aircraft.
Just after 9.45pm on Monday, (December 2), he made his way down the steps to the runway apron on Stansted's northside, which is home to a number of private jet centres accustomed to providing security and privacy for VIP passengers.
Wearing skyscraper stilettos and a Republican red trenchcoat, the first lady, gripped the handrail of the steps tightly and gripped her husband's hand as the pair made their way to the bottom where US ambassador Robert 'Woody' Johnson, owner of the New York Jets American football team, was waiting to welcome them.
The couple were also greeted by the Lord Lieutenant of Essex Jennifer Tolhurst, David Pearey, Foreign Office representative and Stansted's Airport's operations director, Nick Millar.
Usually, the president flies on to the capital in a Marine One, a Sikorsky VH-3D Sea King helicopter known as Marine One when he is on board, alongside at least one decoy with an escort of Chinook choppers.
However, after concerns about bad weather, the couple climbed into the Beast, a £1.2m £1.2m, eight-tonne customised Cadillac capable of withstanding a direct rocket or chemical warfare attack.
They and their entourage swept up the M11 in an impressive motorcade flanked by police outriders. Tight security always surrounds the president. As well as his own United States Secret Service detail, officers from Essex and the Metropolitan police provide protection for his arrival and departure at Stansted.
Mr Trump's three-day state visit in June, which involved more than 6,300 officers, racked up a bill of £3.4m, while his four-day visit in 2018 cost more than £14m.
Both previous trips prompted protests in London and this evening (Tuesday) a demonstration in support of the NHS is expected when Mr Trump and other world leaders attend a reception with the Queen at Buckingham Palace.
The other politicians heading for the NATO summit, at The Grove Hotel at Chandlers Cross near Watford in Herts, who touched down at Stansted include German Chancellor Angela Merkel and Canada's Prime Minister Justin Trudeau.
They were joined by leaders from Slovenia, Greece, Hungary, Netherlands, North Macedonia, Romania and Turkey.


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Friday, February 1, 2019 at 10:00am to 2:00pm
Bowen-Thompson Student Union, 207
Bowen-Thompson Student Union 1001 E Wooster St , Bowling Green, OH 43402
Workshop for women interested in running for political office, or interested in learning more about the political process. Lunch will be provided.
No recent activity
Login to interact with events, personalize your calendar, and get recommendations.


text:
In our retail outlet you will discover the pleasure of shopping directly from the farmer.
Here you will find a great selection of products from Il Colmetto and you will discover and fall in love with flavours from the past.
Closed on Monday and Tuesday
From Wednesday to Saturday 09:00-12:00 and 15:30-19:00
Sunday 10:00-12:00 and 14:00-17:00


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If looking for a quick way to market your product or business, then Google AdWords is the best solution to do so. It just takes a few minutes to set up an AdWords Campaign (its easy too) but the background preparation to make the campaign successful is what we discuss here.
What actually is Google AdWords?
Google allows the advertisers to place their ads on Google Search Results and also on different websites and collect a fee based on the number of ads clicked and number of ads viewed. This is a very effective way to get quick traffic to your site.
A] Steps to be followed to create an AdWords Campaign?
1. First and foremost, do the keyword research of your product using the free AdWords Keyword Suggestion Tool.
2. Note the keywords that are mostly used by the people to search for that product.
3. You can also use the Overture suggestion tool and wordtracker tool to analyze the keywords but the AdWords free tool will just work fine.
4. Now create ad groups for each main keyword or keyphrase. This will enable you to track each keywords efficiency in getting visitors to your site. So you can remove the keywords that do not work and put more effort on the other ones.
5. Check the number of ad campaigns for your product by entering the keywords in the search engine. you will then notice ads displaying on the right side of the search results. If there are only a few ads displayed for your high demand keywords, you have the chance to create a winning ad campaign.
6. Now its time for the main event – Writing successful ad copy. For this purpose, you can get an idea from the other advertisements that appear on Google. Use your main keyword in the title and if possible include it in description too. An effective ad should look like
Google Optimization
Get Qualified Visitors To Your Site
Place Your Ad On Google Today!
You can write 3 lines of ad text with a total of 95 characters. 35 for display URL and 1024 characters limit for actual link of your site.
7. Now you are set ready for the actual creation of the AdWords campaign [completed the background preparation].
8. Test and Test … Use these details in STEP B.
B] How to create a Google AdWords Account?
1. Go o Google.com/AdWords and sign up with your Gmail account.
2. You'll need to pay $ 5 as an activation fee to get started.
3. After that you can choose how much you wish to pay per click and per day.
4. You can choose from a $ 0.05 to $ 50 CPC and daily budget as low as 5 Cents or more.
Ex: If you set your daily budget for $ 50 / day / ad @ 10 cents / click, then you will get a max of 500 clicks per ad. Once your daily budget reached to an end, Google will automatically suspend running your ads until next day.
5. Test your ad campaigns with 3 ad groups, then make necessary changes to your keywords and ad copy. This will give you an idea of which works best of all. You can then keep those settings up and running.
6. Always use a tracking url id for your landing page. This will enable you to track your visitors and their navigated pages. This will also give you an idea whether your ad campaign is working fine or required necessary changes.
Ex: techzene.com/?referrer=Google
7. Now use the details you collected during the STEP A.
All the Best for a Successful Google AdWords Campaign


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(Say goodbye to the Grandyman, kids. He ain't coming back)
With the focus now shifting from behind the plate to the void at second base and need to upgrade the outfield, Cash attempted to keep all options open when he commented on the team's interest in Curtis Granderson last week. Speaking to George King of The Post, Cash said C-Grand is a "serious part" of the Yankees' plans to address the outfield and is "not a fall-back option."
While that all sounds good at face value, the club's actions don't match up to the words. If Granderson is such a serious part of what the Yankees want to do to upgrade their outfield, why was it such a hard decision to make him a qualifying offer earlier this month? Why was the front office still debating whether to make the offer or not in the final hours leading up to the deadline? It's not like the level of production that Granderson had in his last 2 non-injury years weren't worthy of the offer. It's not like he's not on almost equal ground with the Beltrans and Choos of the world when it comes to new contract value. If he's such a big part, why didn't the team extend the qualifying offer and immediate engage him in talks of a new multi-year deal like they did with Cano?
The truth is that Curtis isn't a part of the Yankees' plans. He's exactly what Cash said he isn't, a backup plan. For whatever reason, be it the strikeouts, the lack of a defined outfield position, or the fears of his power declining soon, the Yankees don't value C-Grand as much as they do Beltran and Choo and that's fine. They're allowed to prioritize their offseason targets however they want. Just don't allow yourselves to buy into these lines from Cash though, because they don't ring true when compared to the team's actions. Granderson is the 4th-most important free agent outfielder on the Yankees' list at best, and they're only going to truly go after him if all their other options fall through and sign elsewhere.


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Because of Ease of Use, in today's date mobile apps is fastest mean of accessing a website content and Android is one of leading technology in designing mobile apps
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Striking visual presentations and charismatic online portfolios are absolute musts for models if they want themselves to get noticed. To create a high-quality online modeling portfolio and promote yourself with Future Starr, you want to make the difference and outshine in the modeling industry. And for this promotion, you need not spend big a fortune; just upload your best modeling videos and pictures and raise your audiences and visibility. Upload your photos depicting your different moods with diverse looks, backgrounds, and poses and get yourself noticed by a worldwide audience including; various editors, modeling agencies, bloggers, and fan community while earning extra income.
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- Product Description
- Technical Specification
- Customer Reviews
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Item number PNN7R
Polaroid Originals Everything Box - Polaroid Lab kit Plus 2 packs of filmPhone to Polaroid. 1.Turn pixels into proof. Press Red to remember with the Polaroid Lab. A 3-lens system that acts like a desktop darkroom to transform your digital phone pictures into real Polaroid pictures - in an instant. Something real, something to hold, something to give. Take pictures. Make pictures. Never lose a moment again with the Polaroid Lab. A 3-lens system that acts like a desktop darkroom to transform the digital photos from your phone into real Polaroid pictures - in an instant. 2. Darkrooms just got smaller. The new Polaroid Lab is your very own desktop darkroom. It uses 100% real film chemistry to expose the digital photos on your phone and process them into a Polaroid picture. Something real, something to hold, something to give. 100% real chemistry 80 years of Polaroid film innovation now just a few taps away. The Polaroid Lab uses a 3-lens system to project the screen image from your phone, exposing it onto Polaroid film. Our unique chemical process then develops the image into a Polaroid picture. No printing, no scanning, just an instant formula for timeless images. 3. Take now, make later. Turn that one idea into many with the Polaroid Lab. Using our Polaroid Originals app, you can create seamless collages of up to 9 frames composed in any which way you like. Bring your pictures to life. Our new augmented reality tool brings your memories to life. Using the Polaroid Originals app, you can layer still images with motion. Make for you, or make for someone else. 4. Polaroid pictures now start in your pocket. From something on a screen to tangible thing, the Polaroid Lab brings your digital photos to life.
Technical Specification
|Product Description
|Polaroid Lab - printer - colour - zink
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Waste Electrical and Electronic Equipment (WEEE) and waste batteries must never be placed in your waste disposal or recycling bins. WEEE is taken back free of charge at electrical retail outlets on a one-for-one like-for-like basis. There is a bin for small batteries in your local store. Local authority civic amenity facilities also take back WEEE and waste batteries free of charge. WEEE and waste battery recycling is free. For more detail please see our Policy Pages at www.littlewoodsireland.ie/help/en/weee-directive.page.


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Topic: Faith Must Be Insistent [TREM Devotional 3 December 2019]
Click HERE for Previous MESSAGES by Bishop Mike Okonkwo https://flatimes.com/category/trem-devotional/
"But he answered her not a word. And his disciples came and besought him, saying, Send her away; for she crieth after us." – Matthew 15:23 KJV
Faith must be insistent. If you can believe, Jesus will come through for you. My mind goes to the woman of Canaan that came to Jesus. It is recorded in Matthew 15:21-28. Jesus didn't answer her and then the next thing He said was that it is not good to give the bread of the children to the dogs.' Yet the woman kept on coming. And though it was not time for the Gentiles, Jesus had to change the rule. I believe that the rule is about to change for you today.
The book of Mark 5:35 declares: "While He yet spake, there came from the ruler of the synagogue's house certain which said, thy daughter is dead, why troublest the Master any further?" This was the case of the daughter of Jairus that Jesus had set out to heal, and news came in that she was dead and it was all over. "As soon as Jesus heard the word that was spoken, he saith unto the ruler of the synagogue, be not afraid, only believe"(Mark 5:36).
When Jesus got to the house, He announced to everyone: "…The damsel is not dead, but sleepeth" (Mark 5:39).
Beloved, whatever you have considered dead and impossible in your life is really alive. It is not over for you. The case is not closed. The Father is still on your case.
The folks in the household of Jairus laughed Jesus to scorn. "But when he had put them all out, he taketh the father and the mother of the damsel, and them that were with him, and entereth in where the damsel was lying. And he took the damsel by the hand, and said unto her, Talitha Cumi; which is being interpreted, Damsel, I say unto thee, arise. And straightway, the damsel arose, and walked; for she was of the age of twelve years. And they were astonished with a great astonishment"(Mark 5:40-42).
As long as Jesus is on your case, you should never quit.
Further reading: Matthew 15:21-28
Daily Bible Reading: Morning- Ezekiel 45-46; Evening- 1 John 2
Written by Dr. Mike Okonkwo; Is the Presiding Bishop of The Redeemed Evangelical Mission (TREM); a versatile man of God with over 30 years of dedicated service unto the Lord.
Flatimes' Notice Board: Until you are born again, God ever abiding presence will never be with you. You must be born again to enjoy continuous victory. Please say the displayed prayer below in faith:
Lord Jesus, come into my life. I accept You as my Lord and Personal Saviour. I believe in my heart You died and rose from the dead to save me. Thank You Lord for saving me, in Jesus name Amen.
If you just prayed the prayer of salvation online please send your testimonies and prayer request to firstname.lastname@example.com, Phone: +234 1 773 8584


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Low Carb Dinner Recipes
Collection by FSF - Keto & Low Carb Recipes • Last updated 2 weeks ago
Looking for the best low carb dinner recipes on Pinterest? Check out some of these! I've included easy low carb dinner recipes, quick low carb dinners, crock pot low carb dinners, Instant Pot low carb dinners, and more. There are plenty of low carb dinner ideas on this board to help you with your low carb meal plan!
*EASY!* Keto Chicken Alfredo Recipe! {keto dinner}
This Keto Chicken Alfredo with Broccoli dish couldn't be easier to make and is so good that you won't believe it's keto! Only 5g net carbs per serving.
*SO GOOD!* Keto Buttery Chicken Casserole recipe!!
Looking for an easy-to-assemble keto chicken casserole that is packed with flavor? Look no further than this super tasty Crusted Buttery Chicken Casserole!
*THE BEST!* Keto Chicken Casserole recipes!!
Looking for the yummiest keto chicken casserole recipes on the internet? I've put together seven easy recipes that you won't be able to resist making!
*OH YUM!* Keto CHEESEBURGER Casserole!
This flavorful Keto Cheeseburger Casserole has all the flavors of a cheeseburger without all the carbs! It's easy to make with simple keto staples and will be a huge hit with the whole family.
*OH WOW!* Keto Strawberry Chicken Salad!!
Get ready for one of THE BEST keto salads you've ever tasted! In fact, this Keto Strawberry-Chicken Salad with Maple-Balsamic Vinaigrette may just end up being your favorite.
*SO YUMMY!* Keto PIZZA Casserole recipe!
Looking for a mouthwatering keto casserole recipe the whole family will love? Try this Keto Deep Dish Pepperoni Pizza Casserole!
KETO Chicken Alfredo Casserole!! {keto casserole}
Say hello to this cheesy, creamy keto casserole recipe! Keto Cheesy Chicken Alfredo is ridiculously good and will make your tastebuds sing, guaranteed.
Easy Keto Cheese Casserole! {keto casserole}
If cheese is your love language, you are going to love this cheesy Keto Chicken Broccoli Casserole! It is bursting with cheesy goodnes and flavor.
Keto Appetizer Recipe on a Sheet Pan!
Keto Loaded Oven Roasted Radishes are reminiscent of loaded roasted potatoes topped with creamy ranch dressing, bacon, and cheese.
Keto Teriyaki Casserole: Chicken or Beef
Dig into this amazing Keto Teriyaki Casserole, made with either chicken or beef (your choice!). It is bursting with fresh flavors and makes a great dinner.
Keto Philly Cheesesteak: Keto Dinner Recipe!
You don't need a carb-loaded hoagie roll to enjoy the flavors of Philly Cheesesteak. Instead, try these Philly Cheesesteak Keto Lettuce Wraps!
Keto Egg Roll recipe!!
Missing the delicious flavors of egg rolls? Try this flavorful Keto Egg Roll in a Bowl instead for a mere 3g net carbs per serving!
Easy Keto Chicken Alfredo recipe!!
This Keto Chicken Alfredo with Broccoli dish couldn't be easier to make and is so good that you won't believe it's keto! Only 5g net carbs per serving.
Keto TACO Seasoning recipe!
Taco seasoning packets are loaded with carbs, so it's better to make your own. You will LOVE this tasty homemade Keto Taco Seasoning!
Keto Sheet Pan Chicken!
Looking for a super easy dinner recipe? Look no further than this keto Sheet Pan Chicken Thighs with Roasted Radishes recipe!
Keto Chicken Alfredo Casserole!
Say hello to this cheesy, creamy keto casserole recipe! Keto Cheesy Chicken Alfredo is ridiculously good and will make your tastebuds sing, guaranteed.


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White adipose tissue (WAT) releases fatty acids from stored triacylglycerol for an energy source. Here, we report that targeted deletion of KH-type splicing regulatory protein (KSRP), an RNA-binding protein that regulates gene expression at multiple levels, enhances lipolysis in epididymal WAT (eWAT) because of the upregulation of genes promoting lipolytic activity. Expression of microRNA 145 (miR-145) is decreased because of impaired primary miR-145 processing in Ksrp−/− eWAT. We show that miR-145 directly targets and represses Foxo1 and Cgi58, activators of lipolytic activity, and forced expression of miR-145 attenuates lipolysis. This study reveals a novel in vivo function of KSRP in controlling adipose lipolysis through posttranscriptional regulation of miR-145 expression.
Nutrients providing excess calories are converted to triacylglycerol (TAG) for storage in lipid droplets of white adipose tissue (WAT). The stored TAG is hydrolyzed to release fatty acids, which are crucial for energy production in muscle and other organs during times of demand such as fasting or exercise (1). However, excess TAG accumulation in WAT results in obesity, which increases the risk of diabetes, heart disease, and some forms of cancer. The content of TAG in WAT is determined by the balance of anabolic (esterification of glycerol with fatty acids) and catabolic (lipolytic reactions that hydrolyze TAG to glycerol and fatty acids, referred to as lipolysis) pathways. While the hydrolysis of stored TAG is crucial for providing energy, recent studies have demonstrated that increasing lipolysis in WAT causes an elevation in fatty acid utilization and energy expenditure, thereby protecting against obesity (2, 3). Thus, understanding the regulation of lipolysis in WAT and identification of factors that control this activity may be crucial for the development of therapeutics to prevent obesity and its related disorders.
Three adipocyte lipases are involved in sequential lipolytic reactions and include adipose triglyceride lipase (ATGL) encoded by Pnpla2, hormone-sensitive lipase (HSL) encoded by Lipe, and monoglyceride lipase. ATGL cleaves TAG (4–6), HSL converts diacylglycerol to monoacylglycerol (7), and monoglyceride lipase catalyzes the final step of lipolysis. Lipolysis is tightly controlled by hormones that are secreted according to nutritional status. During fasting, catecholamines bind to β-adrenergic receptors, leading to elevation of cyclic AMP levels and activation of protein kinase A, resulting in stimulation of lipolysis. In contrast, in the fed state, lipolysis is inhibited by insulin (1). In addition to hormones, additional regulators also play critical roles in controlling lipolysis. Transcriptional activation of Pnpla2 by forkhead box O1 (FOXO1) and interferon regulatory factor 4 enhances lipolysis in adipocytes (8, 9). ATGL interacts with regulatory proteins that activate or attenuate its enzyme activity, in which CGI58 (comparative gene identification 58, also referred to as alpha/beta hydrolase domain 5, ABHD5) serves as a coactivator of ATGL activity (10), and G0S2 (G0-G1 switch gene 2) serves as an inhibitor of ATGL (11).
KSRP is a multifunctional RNA-binding protein involved in the posttranscriptional regulation of gene expression, including splicing (12), mRNA decay (13), primary microRNA (pri-miRNA) processing (14), and translation (15). KSRP binds the AU-rich elements (AREs) in the 3′ untranslated regions (UTRs) of inherently unstable mRNAs and promotes their decay by recruiting mRNA decay machineries (13, 16). It also interacts with the terminal loops of a subset of miRNA precursors and promotes their maturation in cultured cells (14). However, the in vivo function of KSRP in controlling pri-miRNA processing has not been completely established. To do this, we have generated Ksrp-null mice (17). Here, we report that lipolysis is elevated in Ksrp−/− eWAT because of enhanced expression of Pnpla2, Lipe, Foxo1, and Cgi58 and expression of miRNA 145 (miR-145) is decreased because of impaired pri-miR-145 processing. Using 3T3-L1 adipocytes, we demonstrate that miR-145 represses lipolysis by targeting Foxo1 and Cgi58 and downregulation of Foxo1 and Cgi58 attenuates lipolysis. Thus, these findings establish KSRP and miR-145 as important negative regulators of lipolysis in WAT.
Animal studies.Generation of Ksrp-null mice in a C57BL/6J background has been described previously (17). Mice were maintained under a 12-h light–12-h dark cycle. All experiments were performed with 10- to 16-week-old male mice. All animal studies were conducted in accordance with the guidelines for animal use and care established by the University of Alabama at Birmingham Animal Resource Program and the Institutional Animal Care and Use Committee.
Isolation of adipocytes and lipolysis assay.Primary adipocytes were isolated from epididymal fat depots by collagenase digestion as described previously (18). Briefly, fat pads were rinsed with phosphate-buffered saline (PBS), minced, and digested for 45 min at 37°C in Krebs-Ringer-HEPES (KRH) buffer (121 mM NaCl, 4.9 mM KCl, 1.2 mM MgSO4, 0.33 mM CaCl2, 12 mM HEPES, pH 7.4) containing 3% bovine serum albumin (BSA) and 1.5 mg/ml type I collagenase. The digested tissues were filtered through a 500-μm metal mesh and centrifuged at 500 × g for 5 min. The floating adipocytes were collected and washed with KRH buffer. Primary adipocytes (1 × 105 cells/ml), tissue explants (∼100 mg), and 3T3-L1 adipocytes were incubated with KRH buffer containing 3% fatty acid-free BSA in the absence or presence of 1 μM isoproterenol at 37°C. The amounts of glycerol and fatty acid (FA) released were determined with free-glycerol reagent (Sigma) and a fatty acid kit (Sigma), respectively.
Measurement of adipocyte numbers and TAG contents.Adipocyte numbers were determined with a hemocytometer. Lipids were extracted from adipocytes in 1% Triton X-100, and TAG contents were determined with Infinity reagent (Thermo Scientific).
Measurement of adipocyte sizes.Epididymal WATs were fixed in PBS containing 10% formalin and embedded in paraffin. Tissue sections were stained with hematoxylin and eosin. Five separate fields were selected for each mouse, and adipocyte sizes were determined with ImageJ software.
mRNA analysis.Total RNA was extracted by TRIzol (Invitrogen). For quantitative real-time RT-PCR analysis, total RNA (1 μg) was reverse transcribed with a mixture of oligo(dT) and random hexamers. Amplification was performed with the Roche LC480 LightCycler and SYBR green system (Roche). mRNA levels were normalized to that of β-actin or cyclophilin mRNA. The sequences of the primers used are listed in Table 1.
miRNA microarrays and analysis.RNA was isolated from eWATs of six wild-type and six Ksrp−/− mutant mice by miRNeasy (Qiagen). Individual RNAs of wild-type and Ksrp−/− mice, respectively, were pooled and subjected to genome-wide miRNA microarray analysis in triplicate performed by Phalanx Biotech. The signals of miRNAs that were 5-fold above the background (these are arbitrarily considered to be expressed in eWAT) and elevated >2-fold in Ksrp−/− eWAT were selected for further analysis. For miR-145 expression analysis, total RNA was converted into cDNA with the miScript II RT kit (Qiagen) and subjected to real-time PCR with a specific primer for miR-145 by using the miScript Primer Assay (Qiagen). miRNA levels were normalized to that of U6 snRNA.
miRNA target prediction.miRNA target prediction was performed by using the miRWalk database (http://www.umm.uni-heidelberg.de/apps/zmf/mirwalk/).
Pri-miRNA in vitro processing assay.A DNA template producing pri-miR-145 was generated by PCR. 32P-labeled pri-miR-145 was synthesized by in vitro transcription and incubated with total extracts of wild-type and Ksrp−/− eWATs in a processing buffer. Pri-miRNA processing assays were performed as described previously (14, 19).
RIP assays.Ribonucleoprotein immunoprecipitation (RIP) assays were performed as described previously (19, 20). Immunoprecipitated pellets were washed, and RNA was isolated, reverse transcribed, and amplified by quantitative PCR (qPCR).
Immunoblotting and antibodies.Proteins were separated by 10% SDS-PAGE and transferred to a polyvinylidene difluoride membrane, which was probed with anti-FOXO1 (Cell Signaling), anti-CGI58 (Abcam), anti-ATGL (Cell Signaling), anti-KSRP (21), anti-α-tubulin (Sigma), and anti-β-actin (Abcam) antibodies.
Cell culture and transfection.3T3-L1 preadipocytes were purchased from the American Type Culture Collection and maintained in Dulbecco's modified Eagle's medium (DMEM) with 10% bovine calf serum (BCS). 3T3-L1 cells were plated in 12-well plates at a density of 80 to 90% confluence and transfected with small interfering RNAs (siRNAs; 60 nM), miRNA mimics (50 nM), or plasmid DNA (1 μg) with 4 μl of Lipofectamine (Invitrogen) in 500 μl of Opti-MEM (Invitrogen) for 6 h the following day. The transfected cells were incubated with DMEM containing 10% BCS for 40 h and induced for differentiation by incubation with DMEM containing 10% FBS, 5 μg/ml insulin, 0.5 mM isobutylmethylxanthine, and 1 μM dexamethasone for 2 days. The transfected cells were transfected with the same siRNA, miRNA, or plasmid again as in the first transfection in Opti-MEM for 6 h. Cells then were cultured in DMEM containing 10% FBS and 5 μg/ml insulin and collected for analysis 5 days after the induction of adipogenesis. For lipolytic gene expression, adipocytes were serum starved for 16 h and stimulated with 1 μM isoproterenol for 2 h. Mouse embryonic fibroblasts (MEFs) were prepared (17), differentiated to adipocytes, and harvested at day 8 for RNA extraction, as well as Oil Red O staining as described previously (22).
Luciferase reporters and assay.Dual-luciferase reporters, expressing firefly and Renilla luciferases and containing the 3′ UTRs of Foxo1 and Cgi58 subcloned downstream of firefly luciferase, and a control reporter, pEZX-MT01, were purchased from GeneCopoeia. The predicted miR-145 target sites were mutated by PCR-mediated site-directed mutagenesis, and mutations were confirmed by DNA sequencing. NIH 3T3 cells were transfected with 250 ng of reporter together with 50 nM miRNA mimic with Lipofectamine. Cells were collected 36 to 48 h after transfection with Luc-Pair miR luciferase assay kits (GeneCopoeia).
miRNA mimics, siRNAs, and plasmid.miR-145 mimic and SiGENOME SMART pool siRNAs against Foxo1 and Cgi58 were purchased from Thermo Scientific. Control miRNA mimic and siRNA were purchased from Qiagen. A plasmid expressing FLAG-KSRP was described previously (17).
Statistical analysis.All data are presented as the mean ± the standard error of the mean (SEM). Statistical significance (P value) was calculated by unpaired two-tailed Student t test.
KSRP ablation causes a reduction in adiposity resulting from decreased TAG content but not impaired adipocyte differentiation.To determine the in vivo function of KSRP, we had previously generated Ksrp−/− mice and found that they had a reduced epididymal fat depot on a chow diet (Fig. 1A). Reduction in adipose tissue mass can result from less TAG storage, impaired adipocyte differentiation, or both. We isolated primary adipocytes from eWAT and determined the total TAG content, which was significantly reduced in Ksrp−/− eWAT (Fig. 1B). Consistent with a decrease in TAG content, adipocytes of Ksrp−/− eWAT were smaller, with a 30% decrease in the mean diameter (Fig. 1C).
To determine whether the reduced adiposity also results from impaired adipocyte differentiation, we examined the expression of adipocyte markers in eWAT of wild-type and Ksrp−/− mice and found no difference in the expression of Pparg and Cebpa, adipogenic transcriptional factors, and Fasn, Fabp4, and Plin2, late adipocyte markers, between the two groups (Fig. 2A). We next examined whether KSRP deficiency affects the adipocyte differentiation of MEFs. Deletion of KSRP did not alter adipocyte differentiation revealed by Oil Red O staining (Fig. 2B), and no difference in the expression of Pparg, Cebpa, fabp4, and Plin2 was detected between wild-type and Ksrp−/− MEFs (Fig. 2C). Altogether, these data suggest that KSRP ablation causes a reduction in TAG content and a smaller adipocyte size in WAT, rather than impaired adipocyte differentiation.
KSRP ablation increases lipolysis and expression of genes involved in fatty acid utilization.A plausible mechanism that leads to reduced TAG content in Ksrp−/− eWAT is enhanced lipolysis. We examined the expression of genes involved in lipolysis in eWAT under fed and fasting conditions. The expression of genes that stimulate lipolysis, including Pnpla2, Lipe, Foxo1, Irf4, and Cgi58, was greater in Ksrp−/− mutant than in wild-type eWAT under both fed and fasting conditions (Fig. 3A). In contrast, no difference in the expression of G0S2, Fabp4, or Plin2 was detected between the groups (Fig. 3A). The levels of the FOXO1, CGI58, and ATGL proteins were also significantly increased in Ksrp−/− mutant eWAT under both fed and fasting conditions (Fig. 3B). The results in Fig. 3B suggested that fasting induced CGI58 and ATGL in wild-type eWAT. However, these samples were analyzed on different blots although immunoblotting was performed at the same time with the same exposure time for each antibody. To further examine whether CGI58 and ATGL are subject to regulation by nutritional states, we repeated the immunoblotting and analyzed their levels in wild-type eWAT on the same blot under fed and fasting conditions. As shown in Fig. 3C, fasting strongly induced CGI58 and ATGL. To correlate gene expression with lipolytic activity, we measured the lipolysis of isolated adipocytes and tissue explants from wild-type and Ksrp−/− mutant eWAT. Glycerol and FA release were elevated in Ksrp−/− mutant adipocytes (Fig. 4A and B) and Ksrp−/− mutant eWAT (Fig. 4C and D) under both basal and isoproterenol-stimulated conditions.
Recent studies have shown that increasing lipolysis also facilitates FA utilization within WAT (2, 3, 23). Consistent with these previous findings, we observed the upregulation of genes involved in thermogenesis and FA oxidation, including Ucp1, Cidea, Cox8b, Acadm, Acadl, Prdm16, Ppara, Ppard, and Ppargc1a, in Ksrp−/− eWAT (Fig. 5). These data indicate that KSRP ablation enhances lipolysis, as well as fat utilization, in eWAT through the upregulation of genes that stimulate lipolysis and mitochondrial FA oxidation.
Reduced miR-145 expression in Ksrp−/− eWAT because of impaired pri-miRNA processing.One of the functions of KSRP is to facilitate the processing of a subset of miRNAs. To determine whether impaired expression of miRNAs plays a role in enhancing lipolysis in Ksrp−/− eWAT, we subjected RNA samples to miRNA microarray analysis and selected miRNAs whose expression was reduced in the absence of KSRP. We identified only one miRNA, miR-145, whose expression was reduced by >2-fold in Ksrp−/− eWAT (see Materials and Methods). We examined miR-145 and pri-miR-145 levels by real-time qPCR and found a decrease in miR-145 levels in Ksrp−/− eWAT under both fed and fasting conditions (Fig. 6A). Fasting increased the levels of miR-145 in wild-type eWAT, but the increase was blunted in Ksrp−/− eWAT (Fig. 6A). In contrast, pri-miR-145 levels (detected with primers P1 and P2, located immediately downstream of pre-miR-145 and shown in Fig. 6B) were increased in Ksrp−/− eWAT under both fed and fasting conditions (Fig. 6C).
To examine whether KSRP regulates the transcription of pri-miR-145, we performed qPCR analysis with primers located in different regions of pri-miR-145. miR-143 and miR-145 are derived from the same bicistronic transcript and are separated by 1.4 kb (Fig. 6B). We found that pri-miR-143 and miR-145 transcript levels detected by primers P3 and P4 (located ∼300 nucleotides upstream of pre-miR-143) were similar between wild-type and Ksrp−/− under both fed and fasting conditions (Fig. 6D). Similar results were obtained with primers located between pre-miR-143 and pre-miR-145 (data not shown). In addition, we observed no difference in the levels of miR-143 between wild-type and Ksrp−/− eWAT (data not shown). Altogether, these results suggest that the transcription of pri-miR-143 and miR-145 is unlikely to be altered in Ksrp−/− eWAT and KSRP regulates miR-145 but not miR-143 expression at the posttranscriptional level.
To support this, we performed RIP assays and observed that KSRP physically associated with pri-miR-145 in wild-type eWAT extracts (Fig. 6E). In vitro pri-miRNA processing assays showed that production of pre-miR-145 was significantly reduced in extracts of Ksrp−/− eWAT (Fig. 6F). Addition of recombinant KSRP to Ksrp−/− extracts restored pre-miR-145 production (Fig. 6G). In contrast, processing of a control pri-miR-23b was equivalent between wild-type and Ksrp−/− eWAT (Fig. 6H). These data suggest that decreased miR-145 expression in Ksrp−/− eWAT is indeed due to a reduction in pri-miR-145 processing.
Downregulation of KSRP in 3T3-L1 adipocytes enhances lipolysis and reduces miR-145 expression.To determine the molecular mechanism that lead to enhanced lipolysis, we used an in vitro adipocyte differentiation model of 3T3-L1 fibroblasts. 3T3-L1 cells were transfected with a control siRNA (siControl) or a KSRP siRNA (siKsrp). After differentiation, lipolysis and expression of lipolytic genes were analyzed. As the isoproterenol-stimulated condition resembles the fasting state, we also examined lipolytic gene expression under this condition. Downregulation of KSRP enhanced lipolysis (Fig. 7B and C) and increased Pnpla2, Lipe, Foxo1, and Cgi58 mRNA levels (Fig. 7D) and FOXO1, CGI58, and ATGL protein levels (Fig. 7A) under both basal and stimulated conditions. While KSRP knockdown did not increase Foxo1 mRNA levels under the basal condition (Fig. 7D), it increased the protein levels (Fig. 7A), suggesting that Foxo1 translation was increased under this condition. In contrast, no difference in the expression of Pparg and Fabp4 was observed upon KSRP knockdown (Fig. 7E), suggesting that KSRP is not required for adipogenesis of 3T3-L1 cells. Similar to the observation in Ksrp−/− eWAT, KSRP knockdown decreased miR-145 levels and increased pri-miR-145 levels under both basal and stimulated conditions (Fig. 7F). While fasting increased miR-145 levels in wild-type eWAT (Fig. 6A), its levels were not increased under the stimulated condition in siControl-treated 3T3-L1 adipocytes (Fig. 7F). This discrepancy is likely due to the differences in cell type and/or signaling pathways between isoproterenol-stimulated 3T3-L1 adipocytes and fasting-stimulating eWAT. These data indicate that elevated lipolysis, as well as decreased miR-145 expression, can be recapitulated in 3T3-L1 adipocytes upon KSRP downregulation.
Overexpression of KSRP reduces FOXO1 and CGI58 and lipolysis and increases miR-145 expression.We next examined whether overexpression of KSRP attenuates lipolysis. Ectopic expression of FLAG-KSRP in 3T3-L1 adipocytes decreased the expression of FOXO1 and CGI58 (Fig. 8A) and increased the levels of miR-145 (Fig. 8B) under both basal and stimulated conditions. As a result of the increase in miR-145, pri-miR-145 levels were moderately decreased (Fig. 8C). More importantly, basal and stimulated lipolysis was significantly attenuated by KSRP overexpression (Fig. 8D). These results indicate that KSRP induces miR-145 expression by promoting pri-miR-145 processing, which decreases the levels of FOXO1 and CGI58 and lipolysis.
Ectopic expression of miR-145 attenuates lipolysis, and miR-145 directly targets Foxo1 and Cgi58.To determine the role of miR-145 in controlling lipolytic gene expression and lipolysis, we overexpressed miR-145 in 3T3-L1 cells transfected with either siControl or siKsrp. Forced expression of miR-145 decreased Pnpla2, Lipe, Foxo1, and Cgi58 (Fig. 9A) but not Fabp4 (Fig. 9B) mRNA levels and FOXO1 and CGI58 protein levels (Fig. 9C) in siControl- and siKsrp-treated adipocytes under both basal and stimulated conditions. Accordingly, ectopic miR-145 expression repressed lipolysis in 3T3-L1 adipocytes treated with siControl and siKsrp under both basal and stimulated conditions (Fig. 9D).
Bioinformatics analysis predicted that Foxo1 and Cgi58 are targets of miR-145, with each 3′ UTR containing a potential target site (Fig. 9E). To verify that miR-145 can directly target Foxo1 and Cgi58 mRNAs, we subcloned their 3′ UTRs into a dual-luciferase reporter. Expression of miR-145 decreased the expression of luciferase reporters harboring the 3′ UTRs of Foxo1 and Cgi58 but not that of a control reporter, MT01, without an insertion (Fig. 9F). Mutations of the target sites in Foxo1 and Cgi58 resisted inhibition by miR-145 (Fig. 9F). Altogether, these data indicate that miR-145 directly regulates the expression of Foxo1 and Cgi58, leading to changes in the expression of Pnpla2 and Lipe and ATGL activity, thus lipolysis.
Downregulation of Foxo1 and Cgi58 attenuates lipolysis.To determine whether elevated lipolysis in the absence of KSRP is due to increased expression of Foxo1 and Cgi58, we downregulated their expression by siRNAs in 3T3-L1 adipocytes treated with either siControl or siKsrp. Downregulation of Foxo1 and Cgi58 decreased lipolysis in both siControl- and siKsrp-treated adipocytes under both basal and stimulated conditions (Fig. 10A). These data indicate that the increase in lipolysis in 3T3-L1 adipocytes upon the downregulation of KSRP is indeed due to increased expression of Foxo1 and Cgi58.
This study shows that targeted deletion of KSRP enhances lipolysis in eWAT through the elevated expression of Foxo1 and Cgi58. We demonstrated that KSRP is involved in the processing of pri-miR-145 in eWAT and that its absence results in the downregulation of miR-145. Mechanistically, miR-145 directly represses Foxo1 and Cgi58. Thus, reduction of miR-145 levels in Ksrp−/− eWAT leads to derepression of these genes, thereby increasing lipolysis. These findings suggest that KSRP is a critical factor for balancing TAG storage and hydrolysis in white adipocytes and that its absence favors hydrolysis partly through the posttranscriptional regulation of miR-145 expression.
FOXO1 is a transcriptional activator of Pnpla2 and stimulates lipolysis (8). It is also required for fasting-induced expression of Irf4, which activates the expression of Pnpla2 and Lipe (9). Thus, elevated expression of Irf4, Pnpla2, and Lipe in Ksrp−/− eWAT is likely due to increased FOXO1. CGI58 (ABHD5) interacts with ATGL and stimulates its TAG hydrolase activity (10). Using adipocytes derived from 3T3-L1 cells, we demonstrated that ectopic expression of miR-145 attenuates Foxo1 and Cgi58, as well as lipolysis, and downregulation of Foxo1 and Cgi58 attenuates lipolysis. These data strongly suggest that enhanced lipolysis in Ksrp−/− eWAT is due to elevated expression of Foxo1 and Cgi58, leading to increased expression of Pnpla2, as well as elevated ATGL activity, and identify a novel function of miR-145 in controlling lipolysis in WAT.
A recent study showed that adipose-tissue-selective overexpression of CGI58 (ABHD5) did not increase lipolysis or protect against diet-induced obesity (24), suggesting that the expression of CGI58 in mouse adipose tissue is not limiting for either basal or stimulated lipolysis. These findings are somewhat contradictory to our hypothesis that increased CGI58 in Ksrp−/− eWAT leads to enhanced lipolysis. It is possible that ATGL levels are also limiting in adipose tissue, which explains that a further increase in CGI58 levels did not enhance ATGL activity, as well as lipolysis, in the study (24). However, we found that both ATGL and CGI58 levels were increased in the absence of KSRP (Fig. 3B and 7A). Hence, we suggest that simultaneous increases in the levels of ATGL and CGI58 result in elevated lipolysis in Ksrp−/− eWAT, consistent with the previous finding that CGI58 activates ATGL activity (10).
We found that pri-miR-145 and miR-145 but not KSRP levels were increased during fasting in wild-type eWAT (Fig. 6A and C and Fig. 3B). These data suggest that the increase in miR-145 levels is due primarily to fasting-induced synthesis of pri-miR145, although we cannot exclude the possibility that the pri-miRNA processing activity of KSRP is also increased during fasting. As fasting increases lipolysis and induces miR-145, which is a negative regulator of lipolysis, we suggest that miR-145 serves as a negative feedback factor to prevent uncontrolled lipolysis during times of demand, such as fasting.
While we have focused entirely on the regulation of FOXO1 and CGI58 by miR-145 in the present study, it is likely that miR-145 also represses other factors that promote lipolysis. Further analysis of miR-145 targets in eWAT should result in the identification of such factors. We also observed the upregulation of genes involved in thermogenesis and mitochondrial FA oxidation in Ksrp−/− eWAT. This upregulation may be due directly to reduced miR-145 expression or result indirectly from increasing lipolysis, which has been shown to increase the expression of these genes (2, 3). Our preliminary analysis showed that overexpression of miR-145 in 3T3-L1 adipocytes repressed the expression of Prdm16, Ppara, Ppard, Ppargc1a, and fatty acid oxidation genes. Interestingly, Prdm16, Ppara, and Ppard are predicted targets of miR-145. Thus, upregulation of these genes in Ksrp−/− eWAT (Fig. 5) is likely due to reduced miR-145 expression. It is also possible that KSRP directly regulates the expression of mRNAs that encode transcriptional regulators critical for fat utilization in eWAT, such as peroxisome proliferator-activated receptor α (PPARα), PPARδ, or PPRAGC1α, through other posttranscriptional mechanisms.
Whereas KSRP has been shown to be required for the processing of a subset of pri-miRNAs in several models of established cell lines through RNA interference-induced downregulation (14, 25), it is somewhat surprising to find that only miR-145 is reduced in Ksrp−/− eWAT by microarray analysis. Other miRNAs previously shown to be regulated by KSRP did not show a difference in Ksrp−/− eWAT in our analysis, although they are clearly expressed in eWAT (data not shown). It is unclear why only miR-145 expression is decreased in eWAT while other KSRP-dependent miRNAs are not. Our findings, together with previous reports (14, 19, 25, 26), suggest a possible cell type or tissue specificity for KSRP-dependent pri-miRNA processing. The function of KSRP in pri-miRNA processing is also likely compensated by its close family members, including FBP1 and FBP3 (27), depending on the cell type. Furthermore, the mechanism by which KSRP promotes pri-miR-145 processing awaits further investigation, although previous data suggest that it interacts with the terminal loop of pre-miRNAs.
While Ksrp−/− mice have a reduced fat mass, it will be of interest to see whether the enhanced lipolysis and fatty acid utilization in WAT are the sole contributions to this phenotype. We also found that Ksrp−/− mice exhibited a reduced body weight, increased expression of brown-fat-selective genes in inguinal WAT, and moderately increased energy expenditure while no differences in activity or food intake were observed (31). These data suggest that the reduction in body adiposity is likely due to increased FA utilization in white adipose tissue. Further studies with adipose-tissue-specific KSRP knockout mice should reveal its role in the control of lipolysis and whole-body adiposity. Nevertheless, our observations are consistent with previous findings that increasing lipolysis in WAT promotes FA oxidation within adipocytes and protects against obesity (2, 3, 23, 28–30). It will also be of interest to examine whether gain- and loss-of-function of miR-145 in adipose tissue affect lipolysis and adiposity in vivo. In summary, this work suggests that modulation of KSRP-dependent pri-miR-145 processing could be a potential therapeutic target for obesity and metabolic disorders.
This work was supported by NIH grant GM068758 (C.-Y.C.) and grants from the Ministero della Salute (RF-2010-2306205) and AICR (10-0527) to R.G.
- Received 9 January 2014.
- Returned for modification 28 January 2014.
- Accepted 6 April 2014.
- Accepted manuscript posted online 14 April 2014.
- Copyright © 2014, American Society for Microbiology. All Rights Reserved.


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Queen's Grandson-in-Law Mike Tindall Wants Prince Harry and Meghan Markle 'to Be Happy' in California
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While he's previously described the process of home-schooling Mia as "really frustrating," he now admits there are some upsides to isolating with your loved ones.
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[Infographic] Why Small Businesses Can (And Should) Hire Big
Startups and small businesses are always advised to think big, but apparently this is even more true when it comes to hiring. While looking for and hiring high potential employees is important for any kind of organization, such hires can be even more critical to the success of a startup.
A high-potential employee tends to be one that not just has ability and ambition, but one that also inspires fellow colleagues and takes charge of any kind of situation – as you can see, these are traits that can make or break a startup that does not have much margin for error as it finds its way to success. Taking the time to find the right high-potential employee can pay great dividends for your business.
Here's an infographic from Next Generation Recruitment on why startup companies should consider hiring someone with "high-potential" for their next job role rather than search long and hard for someone with experience:
[Infographic credit: Next Generation Recruitment]
Daniel Goh is the founder and chief editor of Young | Upstarts, as well as an F&B entrepreneur. Daniel has a background in public relations, and is interested in issues in entrepreneurship, small business, marketing, public relations and the online space. He can be reached at daniel [at] youngupstarts [dot] com.


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Copenhagen Cabbage
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Area Code and Exchange (920) 209 in Wisconsin
Exchange Code 209 for Area Code 920 covers the city of Appleton, Outagamie County in the State of Wisconsin. It is centered at N 44º 15' 42.95", W 88º 24' 55.38". This Exchange Code was introduced on 10 May 1999 and is designated as being used for Wireless telephones.
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In this Exchange Code there are 22 telephone numbers that our research shows belong to legitimate businesses.
Technical Information for Exchange (920) 209
NXX/Exchange Code: 209
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County: Outagamie
State: Wisconsin
Rate Center: APPLETON
Time Zone: CST
DST Observed:
Exchange Status: Active
NXX Intro Date: 10 May 1999
Latitude: 44.2619309
Longitude: -88.4153847
New NPA:
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As the industry's export market development organization, U.S. Wheat Associates (USW) promotes the specific benefits of all six classes of U.S. wheat in competitive markets and works to demonstrate the functional quality, value and reliability of U.S. wheat. USW has an undisputed reputation for transparency and dedication to service. USW strives to be a valuable resource and partner to our export customers, in ways that provide a significant return on farmer and federal investment in wheat export market development.
Recent examples of our work are shared below. Please check back regularly for new success stories.
Market Development Helps Build Future Demand for U.S. Wheat in China
Euromonitor International has predicted that sales of baked goods in the People's Republic of China will increase 22.5% by 2021. Domestic wheat is less than...MORE DETAILS
Trade Service and Visit to the United States Help Increase U.S. Wheat Exports to Colombia
To help Colombian wheat buyers find ways to import more U.S. wheat, USDA Foreign Agricultural Service cooperator U.S. Wheat Associates worked closely with USDA...MORE DETAILS
Trust and Partnership Protect Key North Asian Wheat Export Markets in a Crisis
Just as the 2016 wheat harvest was starting, a farmer in Washington state discovered and reported rogue wheat plants genetically modified to be "Roundup...MORE DETAILS
Reintroducing U.S. Wheat to Angola's Expanding Flour Milling Industry
The West African nation of Angola is making good progress in its desire to improve food security for a rapidly growing population, currently estimated at 24.5...MORE DETAILS
Mexico is a Loyal and Very Important U.S. Wheat Buyer
U.S. Wheat Associates (USW) represents the interests of U.S. wheat farmers in international markets. As it does with all U.S. wheat importing customers, USW...MORE DETAILS


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An Out-of-date Prejudice
The decision of the American Federation of Labour to reject the invitation of the Trade Union Congress to a world trade union con- ference is unfortunate for two reasons. In the first place, it will be a great loss to the conference that so important a part of the American trade union movement should be unrepresented. Secondly, the reason for its abstention is equally to be regretted. The rejection of the invitation is due to the fact that Soviet Labour representatives will be present, the spokesman of the Federation condemning what he described as an attempt " to smuggle Communists into an inter- national meeting through the cellar door." It is disturbing to find leaders of the industrial Labour movement in the United States so persistent in a pre-war attitude of hostility to Soviet trade unionism. No body sending representatives to the conference is committed to anything. It is consultative and exploratory, and no resolutions adopted are binding on any organisation unless it decides to endorse them. It is perfectly true that the Russian trade unions are not free as the British or American unions are, and that their constitution is on a very different basis. But there is no good reason why trade unions with different constitutions should not discuss matters of common interest, just as Governments in differently constituted States confer together. It is true that Russian attempts at interven- tion in foreign labour movements have in the past been provocative and often obnoxious. But there have been fundamental changes in recent years. There is every reason for hope that the causes of friction may be removed, but such hope could not be realised if the Labour movements in other countries insisted on cold-shouldering the representatives of Russia and actually shutting the door on con- sultation. This is a disastrous approach to the problem of international. co-operation.