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AT#139 - Travel to Lancaster County Pennsylvania

Lancaster County Pennsylvania




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AT#163 - Travel to the Yucatan Peninsula of Mexico

The Amateur Traveler talks to Zora O'Neil who is one of the co-authors of the Rough Guide in the Yucatan guide book. Zora talks about this very beautiful, very tropical and very isolated part of Mexico. Learn about the beach communities (Riviera Maya - Cancun, Talum, Playa del Carmen; Costa Maya - Majahual, Xcalak; Isla Holbox), getting around, the food (Xni Pec, Achiote), the colonial cities (Merida) and the Mayan ruins (the Ruta Puc, Uxmal, Calakmul).




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AT#193 - Independent Travel to Beijing, China

The Amateur Traveler talks to Lee from Atlanta who is currently living in Qing Dao, China about traveling independently in Beijing, China. Lee describes getting around by bus, subway and taxi, eating street food, and biking through the Hutongs of Beijing. He guides us to lesser known sites like Beijing’s underground city and the site of the old Summer Palace. He leads us to the great wall at Badaling, Mutianyu, and Simatai. Lee also talks about side trips to see the Buddhas in the Yungang Caves near Datong and the nearby hanging monasteries and to see the Qing royal villas and replica of the Lhasa temple in Chungde. We talk about where to find a guide (and why you may not need one), Chinese history and what Lee suggested his parents should bring to China.




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AT#259 - Travel to Pittsburgh, Pennsylvania

The Amateur Traveler talks to Chris Bogdon who talks to us about his hometown of Pittsburgh, Pennsylvania. This former steel capital has undergone a renaissance since its steel business went away and Chris tells us some of the reasons to visit this city at the headwaters of the Ohio River. Pittsburgh boasts both historic Fort Pitt and nearby Fort Necessity where George Washington made a name for himself. It is the home to many different ethnic neighborhoods which it celebrates with food and festivals and commemorates in an Immigration Museum in the Carnegie Library of the University of Pittsburgh. The town now hosts students in greater numbers than steelworkers. It is near Frank Lloyd Wright's Fallingwaters and a wine region. Chris also talks about side trips to Bethlehem, PA and Jim Thorpe, PA.




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AT#264 - Travel to Aspen, Colorado

The Amateur Traveler talks to Kara Williams of TheVacationGals.com about Aspen, Colorado. Like so many locals who live in that area of Colorado, Kara came for the winters but stayed for the summers. She tells us about this historic silver-mining town that is better known as a winter playground for the wealthy now than for its mining past. Whether you are skiing, hiking or fly fishing it has a wealth of outdoor activities. It offers great, if not always inexpensive, food and a wealth of artistic events set in a gorgeous mountain valley. Kara describes side trips to the Ghost towns of Ashcroft and Independence, to the continental divide at Independence Pass and to the caves at The Grottos. She also tells you whether the Aspen Crud is something you want to get. Aspen also hosts festivals as diverse as the Aspen Institute, Jazz Aspen Snowmass, the Aspen Music Festival and School and Aspen Summer Words.




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AT#462 - Travel to Philadelphia, Pennsylvania

Hear about travel to Philadelphia, Pennsylvania as the Amateur Traveler talks to Larissa and Michael Milne of changesinlongitude.com. They recently authored the "Philadelphia Liberty Trail" book.

 




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AT#484 - Travel to Mackinac Island (and Michigan's Upper Peninsula)

Hear about travel to Michigan's Upper Peninsula (the UP)  as the Amateur Traveler talks to Jennifer Schuitema from Grand Rapids Michigan about travel to the northern remote part of the Great Lake State.

 




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AT#553 - Travel to the Kenai Peninsula, Alaska

Hear about travel to Alaska's Kenai Peninsula as the Amateur Traveler talks to tour guide Mareth Griffith about her adopted home. 




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AT#602 - Travel to Merida and the Yucatan Peninsula of Mexico

Hear about travel to Merida and the Yucatan Peninsula as the Amateur Traveler talks to Tommo & Megsy from foodfuntravel.com about their recent homebase.




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AT#621 - Travel to Pittsburgh and Western Pennsylvania

Hear about travel to Pittsburgh and Western Pennsylvania as the Amateur Traveler talks to Tom Shaner about his hometown.




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He Spent 45 Years in Prison for Crime He Didn’t Commit, Turned to Art as His Escape

In 1971, a man named Gregory Harris was murdered. Richard Phillips, an autoworker, was convicted of the crime and spent the next 45 years in prison. The problem? Phillips was innocent. Instead, it was the star witness during the trial who framed Phillips, and it took his alleged partner-in-crime, Richard Polombo, decades to admit that…

The post He Spent 45 Years in Prison for Crime He Didn’t Commit, Turned to Art as His Escape appeared first on The Western Journal.




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Florida Fishermen Nab 6-Foot Bull Shark During First Weekend of Reopened Beaches

Everybody wanted to get to the shore last weekend when the state of Florida reopened its beaches. But one of the beachgoers who came in for some extra attention was a six-foot-long bull shark caught near Navarre Beach, according to WKRG-TV. Video shot by Shelley Goudy of Fort Walton showed several men gathered around the…

The post Florida Fishermen Nab 6-Foot Bull Shark During First Weekend of Reopened Beaches appeared first on The Western Journal.




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An Open Letter To American Corporations: It’s Good Business (and Smart Marketing) To Support Quality Journalism

“Outbreaks have sparked riots and propelled public-health innovations, prefigured revolutions and redrawn maps.” – The New Yorker, April 2020 “Nothing will be the same.”  That’s the overwhelming takeaway I’ve heard from dozens of conversations I’ve had with C-suite leaders, physicians, policy experts and media professionals these past few weeks.  When it comes to the business … Continue reading "An Open Letter To American Corporations: It’s Good Business (and Smart Marketing) To Support Quality Journalism"




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For Some Refugees, Safe Haven Now Depends on a DNA Test

Changes to a program designed to reunite refugees with family in the U.S. have slowed -- and in some cases outright denied -- legitimate entries into the country.




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Pentagon Opens Probe Into Sexual Abuse by U.S. Allies in Afghanistan

The Defense Department's Inspector General has opened an investigation into whether U.S. troops were discouraged from reporting the rape and sexual abuse of children by their Afghan allies.




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What Happens When Police Are Forced to Reform?

The Justice Department has intervened in troubled police departments for 20 years. Are reform efforts working?




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Apple to begin reopening U.S. stores this month

Apple, dear reader, has been missing you — and it's banking on the fact that you've been missing the opportunity to touch its products before you buy them, too. 

In an effort to ease this assuredly mutual feeling of longing, the company confirmed on Friday plans to begin reopening some of its U.S. stores as early as MondayApple had been aiming for a May reopening for some time, but now it's official. 

So reports CNBC, which notes that the openings are, for now, limited to stores in four states: Idaho, South Carolina, Alabama, and Alaska.

"We've missed our customers and look forward to offering our support," an Apple spokesperson told CNN BusinessRead more...

More about Apple, Coronavirus, Tech, and Big Tech Companies





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Pence aide tests positive for coronavirus

CNBC reports that an aide to Pence has tested positive for COVID-19. This follows yesterday's report that Trump's personal valet tested positive for the virus.

A spokeswoman for Pence did not immediately respond to CNBC’s request for comment.

Pence was scheduled to travel to Des Moines, Iowa, in the morning, but his departure from Andrews Air Force Base was delayed by nearly an hour as staff dealt with news of the diagnosis. Reporters traveling with Pence said several staffers disembarked from Air Force Two just before takeoff.

Photo of Pence: Know Your Meme Read the rest





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Newsroom: Coronavirus Hits China Ad Spending

eMarketer cuts forecast for total media ad spending by 6.2%   March 17, 2020 (New York, NY) – Just months after the first case was reported, it is already clear […]




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Newsroom: COVID-19 Boosts UK Time Spent with Media

TV time among adult viewers up 10 minutes per day in 2020 April 23, 2020 (London, UK) – The UK’s social distancing measures due to coronavirus are having a measurable […]




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Newsroom: Time Spent with Media in China Grows amid COVID-19 Pandemic

Our Estimate for Time Spent with TV in 2020 Is Revised Upward by 5 Minutes April 24, 2020 (New York, NY) – Over the course of just a few months, […]




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Oscars race wide open

Part of the Going for gold promo for the BBC UK Homepage




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Garden centres and nurseries reopen to lineups of anxious customers

The Ontario government gave garden centres and nurseries the green light to open their doors to the public on Friday.




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Police find 8-foot boa constrictor while investigating Oppenheimer Park fight

Police officers responding to a call about a man with a machete in Oppenheimer Park Friday afternoon found what they were looking for, and then some.




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Too soon? B.C. workers, employers struggle with thorny reopening issues

As British Columbians digest the implications in the steps the premier announced in reopening the province's economy, some residents have come to the conclusion they’re too much too soon.




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Campers must clear out of Oppenheimer Park by noon Saturday

With the eviction date looming for campers to leave Oppenheimer Park, B.C.'s social development minister says everyone is still expected to be out of the park by Saturday.




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MI Barber Shop Owner Defies Gov. Whitmer Shutdown Order…Opens Business…Police Officer Walks In…Says, “I love you!”…Walks Out

The following article, MI Barber Shop Owner Defies Gov. Whitmer Shutdown Order…Opens Business…Police Officer Walks In…Says, “I love you!”…Walks Out, was first published on 100PercentFedUp.com.

Last week, we reported about how Shelley Luther, owner of the Salon Á La Mode in North Dallas, Texas, who opened up her business in defiance of lockdown orders in the city. The salon owner said that she was ignoring a citation and a cease and desist order from the city to shut down. This one […]

Continue reading: MI Barber Shop Owner Defies Gov. Whitmer Shutdown Order…Opens Business…Police Officer Walks In…Says, “I love you!”…Walks Out ...




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77-Yr-Old MI Barber Defies Gov Whitmer’s Shutdown Order: ”I don’t need another mother” Shop Will Stay Open Until “Jesus walks in or until they arrest me” [VIDEO]

The following article, 77-Yr-Old MI Barber Defies Gov Whitmer’s Shutdown Order: ”I don’t need another mother” Shop Will Stay Open Until “Jesus walks in or until they arrest me” [VIDEO], was first published on 100PercentFedUp.com.

Emergency orders that “non-essential businesses” remain closed during the Covid-19 crisis have devastated small business owners across America. A wave of business owners across the nation are defying executive orders by their governors and opening their businesses anyhow. Yesterday, we reported about a small business owner in the state of Michigan, where Governor Gretchen Whitmer […]

Continue reading: 77-Yr-Old MI Barber Defies Gov Whitmer’s Shutdown Order: ”I don’t need another mother” Shop Will Stay Open Until “Jesus walks in or until they arrest me” [VIDEO] ...




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Breaking: Texas AG Calls for Immediate Release of Salon Owner Jailed for Opening…Texas Lt Gov Offers to Pay Salon Owner’s $7k Fine

The following article, Breaking: Texas AG Calls for Immediate Release of Salon Owner Jailed for Opening…Texas Lt Gov Offers to Pay Salon Owner’s $7k Fine, was first published on 100PercentFedUp.com.

Salon A La Mode owner Shelley Luther opened her salon in defiance of the lockdown order for salons to stay closed during the coronavirus crisis. She boldly ripped. up the citation she was given by the police and refused to shut her doors. Luther hired a lawyer and went to court where an activist judge […]

Continue reading: Breaking: Texas AG Calls for Immediate Release of Salon Owner Jailed for Opening…Texas Lt Gov Offers to Pay Salon Owner’s $7k Fine ...




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BREAKING: Vice President Mike Pence’s Press Sec Katie Miller, Wife of President Trump’s Sr. Advisor, Stephen Miller, Tests Positive For COVID-19

The following article, BREAKING: Vice President Mike Pence’s Press Sec Katie Miller, Wife of President Trump’s Sr. Advisor, Stephen Miller, Tests Positive For COVID-19, was first published on 100PercentFedUp.com.

Only moments ago, White House Press Secretary Kayleigh McEnany confirmed that a member of Vice President Mike Pence’s team tested positive for coronavirus. Watch: White House Press Secretary Kayleigh McEnany confirms a member of Vice President Mike Pence's team tested positive for coronavirus pic.twitter.com/3VaUXbwMq7 — Bloomberg QuickTake (@QuickTake) May 8, 2020 Reuters White House Correspondent […]

Continue reading: BREAKING: Vice President Mike Pence’s Press Sec Katie Miller, Wife of President Trump’s Sr. Advisor, Stephen Miller, Tests Positive For COVID-19 ...




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Busted! Late-Night Hack Comedian, Jimmy Kimmel Is Forced To Apologize For Sharing Highly Edited Video Of VP Pence To Make Him Look Bad

The following article, Busted! Late-Night Hack Comedian, Jimmy Kimmel Is Forced To Apologize For Sharing Highly Edited Video Of VP Pence To Make Him Look Bad, was first published on 100PercentFedUp.com.

Last night, Jimmy Kimmel, host of the low-rated, late-night Jimmy Kimmel Show, shared a deceptively edited video clip of Vice President Pence delivering PPE to a nursing home. Today, liberal activist Matt McDermott tweeted the videotaped segment on VP Pence that was edited to make the vice president look like he was faking a delivery […]

Continue reading: Busted! Late-Night Hack Comedian, Jimmy Kimmel Is Forced To Apologize For Sharing Highly Edited Video Of VP Pence To Make Him Look Bad ...




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Rush Limbaugh Predicts Joe Biden Won’t Be The Dem Nominee: “Something’s Gonna Happen”

The following article, Rush Limbaugh Predicts Joe Biden Won’t Be The Dem Nominee: “Something’s Gonna Happen”, was first published on 100PercentFedUp.com.

Is Joe Biden going to become the Democrat nominee and run against Trump in the fall?

Continue reading: Rush Limbaugh Predicts Joe Biden Won’t Be The Dem Nominee: “Something’s Gonna Happen” ...




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Obama Private Call Released: Implores Political Operatives to Help Protect Him…”We gotta make this happen”

The following article, Obama Private Call Released: Implores Political Operatives to Help Protect Him…”We gotta make this happen”, was first published on 100PercentFedUp.com.

Michael Isikoff at Yahoo News on Friday night released audio of a call from former President Barack Obama to political operatives and the media to help protect “the rule of law” by protecting him. Obama desperately wants the Deep State and media to protect him by helping elect Joe Biden: “The fact that there is […]

Continue reading: Obama Private Call Released: Implores Political Operatives to Help Protect Him…”We gotta make this happen” ...




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Owners of new retail cannabis store hoping to open soon in Pillette Village

At a time when store front vacancies are growing thanks to COVID-19, a new retail cannabis store in Pillette Village is hoping to open soon.




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Provincial parks will reopen but for day-use only

Ontario’s provincial parks and conservation areas will reopen this week but campgrounds and beaches will continue to be off-limits for now.




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'Quaranscream': Wine spritzer company opens Mother's Day venting hotline

A beverage company in the U.S. is inviting moms to let out a ‘quaranscream’ this Mother’s Day on a designated ‘zero-judgement venting hotline’ for a chance to win its wine spritzers.




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COVID-19: How Do We Re-open the Economy?

21 April 2020

Creon Butler

Research Director, Trade, Investment & New Governance Models: Director, Global Economy and Finance Programme
Following five clear steps will create the confidence needed for both the consumer and business decision-making which is crucial to a strong recovery.

2020-04-21-Shop-Retail-Closed

Chain wrapped around the door of a Saks Fifth Avenue Inc. store in San Francisco, California, during the COVID-19 crisis. Photo by David Paul Morris/Bloomberg via Getty Images

With the IMF forecasting a 6.1% fall in advanced economy GDP in 2020 and world trade expected to contract by 11%, there is intense focus on the question of how and when to re-open economies currently in lockdown.

But no ‘opening up’ plan has a chance of succeeding unless it commands the confidence of all the main actors in the economy – employees, consumers, firms, investors and local authorities.

Without public confidence, these groups may follow official guidance only sporadically; consumers will preserve cash rather than spend it on goods and services; employees will delay returning to work wherever possible; businesses will face worsening bottlenecks as some parts of the economy open up while key suppliers remain closed; and firms will continue to delay many discretionary investment and hiring decisions.

Achieving public confidence

Taken together, these behaviours would substantially reduce the chances of a strong economic bounce-back even in the absence of a widespread second wave of infections. Five key steps are needed to achieve a high degree of public confidence in any reopening plan.

First, enough progress must be made in suppressing the virus and in building public health capacity so the public can be confident any new outbreak will be contained without reverting to another full-scale lockdown. Moreover, the general public needs to feel that the treatment capacity of the health system is at a level where the risk to life if someone does fall ill with the virus is at an acceptably low level.

Achieving this requires the government to demonstrate the necessary capabilities - testing, contact tracing, quarantine facilities, supplies of face masks and other forms of PPE (personal protective equipment) - are actually in place and can be sustained, rather than relying on future commitments. It also needs to be clear on the role to be played going forward by handwashing and other personal hygiene measures.

Second, the authorities need to set out clear priorities on which parts of the economy are to open first and why. This needs to take account of both supply side and demand side factors, such as the importance of a particular sector to delivering essential supplies, a sector’s ability to put in place effective protocols to protect its employees and customers, and its importance to the functioning of other parts of the economy. There is little point in opening a car assembly plant unless its SME suppliers are able to deliver the required parts.

Detailed planning of the phasing of specific relaxation measures is essential, as is close cooperation between business and the authorities. The government also needs to establish a centralised coordination function capable of dealing quickly with any unexpected supply chain glitches. And it must pay close attention to feedback from health experts on how the process of re-opening the economy sector-by-sector is affecting the rate of infection.  

Third, the government needs to state how the current financial and economic support measures for the economy will evolve as the re-opening process continues. It is critical to avoid removing support measures too soon, and some key measures may have to continue to operate even as firms restart their operations. It is important to show how - over time - the measures will evolve from a ‘life support’ system for businesses and individuals into a more conventional economic stimulus.

This transition strategy could initially be signalled through broad principles, but the government needs to follow through quickly by detailing specific measures. The transition strategy must target sectors where most damage has been done, including the SME sector in general and specific areas such as transport, leisure and retail. It needs to factor in the hard truth that some businesses will be no longer be viable after the crisis and set out how the government is going to support employees and entrepreneurs who suffer as a result.

The government must also explain how it intends to learn the lessons and capture the upsides from the crisis by building a more resilient economy over the longer term. Most importantly, it has to demonstrate continued commitment to tackling climate change – which is at least as big a threat to mankind’s future as pandemics.

Fourth, the authorities should explain how they plan to manage controls on movement of people across borders to minimise the risk of new infection outbreaks, but also to help sustain the opening-up measures. This needs to take account of the fact that different countries are at different stages in the progress of the pandemic and may have different strategies and trade-offs on the risks they are willing to take as they open up.

As a minimum, an effective border plan requires close cooperation with near neighbours as these are likely to be the most important economic counterparts for many countries. But ideally each country’s plan should be part of a wider global opening-up strategy coordinated by the G20. In the absence of a reliable antibody test, border control measures will have to rely on a combination of imperfect testing, quarantine, and new, shared data requirements for incoming and departing passengers.  

Fifth, the authorities must communicate the steps effectively to the public, in a manner that shows not only that this is a well thought-through plan, but also does not hide the extent of the uncertainties, or the likelihood that rapid modifications may be needed as the plan is implemented. In designing the communications, the authorities should develop specific measures to enable the public to track progress.

Such measures are vital to sustaining business, consumer and employee confidence. While some smaller advanced economies appear close to completing these steps, for many others there is still a long way to go. Waiting until they are achieved means higher economic costs in the short-term. But, in the long-term, they will deliver real net benefits.

Authorities are more likely to sustain these measures because key economic actors will actually follow the guidance given. Also, by instilling confidence, the plan will bring forward the consumer and business decision-making crucial to a strong recovery. In contrast, moving ahead without proper preparation risks turning an already severe economic recession into something much worse.




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Prince Harry Opens the Stavros Niarchos Foundation Floor

16 June 2017

Prince Harry visited Chatham House on 15 June to open the Stavros Niarchos Foundation Floor.

His Royal Highness met with young fellows from the Queen Elizabeth II Academy for Leadership in International Affairs and discussed the important role that the next generation of leaders must play in bringing about positive change in their communities. 

The Academy was formally launched by Her Majesty The Queen at Chatham House in 2014.

Prince Harry also contributed to the first scenario exercise held in the institute’s new simulation centre, which explored how to respond to a humanitarian emergency that required landmine clearance, drawing on the prince’s work in the field of landmine eradication.

The opening of the Stavros Niarchos Foundation Floor marks a significant moment in the modern history of the institute and is a core component of the Chatham House Second Century Initiative, which aims to strengthen the institute’s capacity to innovate and meet the growing demand for its research in the lead-up to its centenary in 2020.

The extension includes a series of new facilities, including the Asfari Centre for Academy Fellows, the simulation centre, new meeting spaces and a media studio, which will ensure that Chatham House can continue to contribute to building a sustainably secure, prosperous and just world over the coming decades.

Mine Action in Angola: Landmine-Free by 2025

HM The Queen Launches Academy for Leadership




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Institutionalization, path dependence and the persistence of the Anglo- American special relationship

1 September 2016 , Volume 92, Number 5

Ruike Xu




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COVID-19: How Do We Re-open the Economy?

21 April 2020

Creon Butler

Research Director, Trade, Investment & New Governance Models: Director, Global Economy and Finance Programme
Following five clear steps will create the confidence needed for both the consumer and business decision-making which is crucial to a strong recovery.

2020-04-21-Shop-Retail-Closed

Chain wrapped around the door of a Saks Fifth Avenue Inc. store in San Francisco, California, during the COVID-19 crisis. Photo by David Paul Morris/Bloomberg via Getty Images

With the IMF forecasting a 6.1% fall in advanced economy GDP in 2020 and world trade expected to contract by 11%, there is intense focus on the question of how and when to re-open economies currently in lockdown.

But no ‘opening up’ plan has a chance of succeeding unless it commands the confidence of all the main actors in the economy – employees, consumers, firms, investors and local authorities.

Without public confidence, these groups may follow official guidance only sporadically; consumers will preserve cash rather than spend it on goods and services; employees will delay returning to work wherever possible; businesses will face worsening bottlenecks as some parts of the economy open up while key suppliers remain closed; and firms will continue to delay many discretionary investment and hiring decisions.

Achieving public confidence

Taken together, these behaviours would substantially reduce the chances of a strong economic bounce-back even in the absence of a widespread second wave of infections. Five key steps are needed to achieve a high degree of public confidence in any reopening plan.

First, enough progress must be made in suppressing the virus and in building public health capacity so the public can be confident any new outbreak will be contained without reverting to another full-scale lockdown. Moreover, the general public needs to feel that the treatment capacity of the health system is at a level where the risk to life if someone does fall ill with the virus is at an acceptably low level.

Achieving this requires the government to demonstrate the necessary capabilities - testing, contact tracing, quarantine facilities, supplies of face masks and other forms of PPE (personal protective equipment) - are actually in place and can be sustained, rather than relying on future commitments. It also needs to be clear on the role to be played going forward by handwashing and other personal hygiene measures.

Second, the authorities need to set out clear priorities on which parts of the economy are to open first and why. This needs to take account of both supply side and demand side factors, such as the importance of a particular sector to delivering essential supplies, a sector’s ability to put in place effective protocols to protect its employees and customers, and its importance to the functioning of other parts of the economy. There is little point in opening a car assembly plant unless its SME suppliers are able to deliver the required parts.

Detailed planning of the phasing of specific relaxation measures is essential, as is close cooperation between business and the authorities. The government also needs to establish a centralised coordination function capable of dealing quickly with any unexpected supply chain glitches. And it must pay close attention to feedback from health experts on how the process of re-opening the economy sector-by-sector is affecting the rate of infection.  

Third, the government needs to state how the current financial and economic support measures for the economy will evolve as the re-opening process continues. It is critical to avoid removing support measures too soon, and some key measures may have to continue to operate even as firms restart their operations. It is important to show how - over time - the measures will evolve from a ‘life support’ system for businesses and individuals into a more conventional economic stimulus.

This transition strategy could initially be signalled through broad principles, but the government needs to follow through quickly by detailing specific measures. The transition strategy must target sectors where most damage has been done, including the SME sector in general and specific areas such as transport, leisure and retail. It needs to factor in the hard truth that some businesses will be no longer be viable after the crisis and set out how the government is going to support employees and entrepreneurs who suffer as a result.

The government must also explain how it intends to learn the lessons and capture the upsides from the crisis by building a more resilient economy over the longer term. Most importantly, it has to demonstrate continued commitment to tackling climate change – which is at least as big a threat to mankind’s future as pandemics.

Fourth, the authorities should explain how they plan to manage controls on movement of people across borders to minimise the risk of new infection outbreaks, but also to help sustain the opening-up measures. This needs to take account of the fact that different countries are at different stages in the progress of the pandemic and may have different strategies and trade-offs on the risks they are willing to take as they open up.

As a minimum, an effective border plan requires close cooperation with near neighbours as these are likely to be the most important economic counterparts for many countries. But ideally each country’s plan should be part of a wider global opening-up strategy coordinated by the G20. In the absence of a reliable antibody test, border control measures will have to rely on a combination of imperfect testing, quarantine, and new, shared data requirements for incoming and departing passengers.  

Fifth, the authorities must communicate the steps effectively to the public, in a manner that shows not only that this is a well thought-through plan, but also does not hide the extent of the uncertainties, or the likelihood that rapid modifications may be needed as the plan is implemented. In designing the communications, the authorities should develop specific measures to enable the public to track progress.

Such measures are vital to sustaining business, consumer and employee confidence. While some smaller advanced economies appear close to completing these steps, for many others there is still a long way to go. Waiting until they are achieved means higher economic costs in the short-term. But, in the long-term, they will deliver real net benefits.

Authorities are more likely to sustain these measures because key economic actors will actually follow the guidance given. Also, by instilling confidence, the plan will bring forward the consumer and business decision-making crucial to a strong recovery. In contrast, moving ahead without proper preparation risks turning an already severe economic recession into something much worse.




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The mRNA levels of heat shock factor 1 are regulated by thermogenic signals via the cAMP-dependent transcription factor ATF3 [Metabolism]

Heat shock factor 1 (HSF1) regulates cellular adaptation to challenges such as heat shock and oxidative and proteotoxic stresses. We have recently reported a previously unappreciated role for HSF1 in the regulation of energy metabolism in fat tissues; however, whether HSF1 is differentially expressed in adipose depots and how its levels are regulated in fat tissues remain unclear. Here, we show that HSF1 levels are higher in brown and subcutaneous fat tissues than in those in the visceral depot and that HSF1 is more abundant in differentiated, thermogenic adipocytes. Gene expression experiments indicated that HSF1 is transcriptionally regulated in fat by agents that modulate cAMP levels, by cold exposure, and by pharmacological stimulation of β-adrenergic signaling. An in silico promoter analysis helped identify a putative response element for activating transcription factor 3 (ATF3) at −258 to −250 base pairs from the HSF1 transcriptional start site, and electrophoretic mobility shift and ChIP assays confirmed ATF3 binding to this sequence. Furthermore, functional assays disclosed that ATF3 is necessary and sufficient for HSF1 regulation. Detailed gene expression analysis revealed that ATF3 is one of the most highly induced ATFs in thermogenic tissues of mice exposed to cold temperatures or treated with the β-adrenergic receptor agonist CL316,243 and that its expression is induced by modulators of cAMP levels in isolated adipocytes. To the best of our knowledge, our results show for the first time that HSF1 is transcriptionally controlled by ATF3 in response to classic stimuli that promote heat generation in thermogenic tissues.




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Inflammatory and mitogenic signals drive interleukin 23 subunit alpha (IL23A) secretion independent of IL12B in intestinal epithelial cells [Signal Transduction]

The heterodimeric cytokine interleukin-23 (IL-23 or IL23A/IL12B) is produced by dendritic cells and macrophages and promotes the proinflammatory and regenerative activities of T helper 17 (Th17) and innate lymphoid cells. A recent study has reported that IL-23 is also secreted by lung adenoma cells and generates an inflammatory and immune-suppressed stroma. Here, we observed that proinflammatory tumor necrosis factor (TNF)/NF-κB and mitogen-activated protein kinase (MAPK) signaling strongly induce IL23A expression in intestinal epithelial cells. Moreover, we identified a strong crosstalk between the NF-κB and MAPK/ERK kinase (MEK) pathways, involving the formation of a transcriptional enhancer complex consisting of proto-oncogene c-Jun (c-Jun), RELA proto-oncogene NF-κB subunit (RelA), RUNX family transcription factor 1 (RUNX1), and RUNX3. Collectively, these proteins induced IL23A secretion, confirmed by immunoprecipitation of endogenous IL23A from activated human colorectal cancer (CRC) cell culture supernatants. Interestingly, IL23A was likely secreted in a noncanonical form, as it was not detected by an ELISA specific for heterodimeric IL-23 likely because IL12B expression is absent in CRC cells. Given recent evidence that IL23A promotes tumor formation, we evaluated the efficacy of MAPK/NF-κB inhibitors in attenuating IL23A expression and found that the MEK inhibitor trametinib and BAY 11–7082 (an IKKα/IκB inhibitor) effectively inhibited IL23A in a subset of human CRC lines with mutant KRAS or BRAFV600E mutations. Together, these results indicate that proinflammatory and mitogenic signals dynamically regulate IL23A in epithelial cells. They further reveal its secretion in a noncanonical form independent of IL12B and that small-molecule inhibitors can attenuate IL23A secretion.




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Extending the Limits of Quantitative Proteome Profiling with Data-Independent Acquisition and Application to Acetaminophen-Treated Three-Dimensional Liver Microtissues

Roland Bruderer
May 1, 2015; 14:1400-1410
Research




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Targeted Data Extraction of the MS/MS Spectra Generated by Data-independent Acquisition: A New Concept for Consistent and Accurate Proteome Analysis

Ludovic C. Gillet
Jun 1, 2012; 11:O111.016717-O111.016717
Research




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The cytochrome P450 enzyme CYP24A1 increases proliferation of mutant KRAS-dependent lung adenocarcinoma independent of its catalytic activity [Cell Biology]

We previously reported that overexpression of cytochrome P450 family 24 subfamily A member 1 (CYP24A1) increases lung cancer cell proliferation by activating RAS signaling and that CYP24A1 knockdown inhibits tumor growth. However, the mechanism of CYP24A1-mediated cancer cell proliferation remains unclear. Here, we conducted cell synchronization and biochemical experiments in lung adenocarcinoma cells, revealing a link between CYP24A1 and anaphase-promoting complex (APC), a key cell cycle regulator. We demonstrate that CYP24A1 expression is cell cycle–dependent; it was higher in the G2-M phase and diminished upon G1 entry. CYP24A1 has a functional destruction box (D-box) motif that allows binding with two APC adaptors, CDC20-homologue 1 (CDH1) and cell division cycle 20 (CDC20). Unlike other APC substrates, however, CYP24A1 acted as a pseudo-substrate, inhibiting CDH1 activity and promoting mitotic progression. Conversely, overexpression of a CYP24A1 D-box mutant compromised CDH1 binding, allowing CDH1 hyperactivation, thereby hastening degradation of its substrates cyclin B1 and CDC20, and accumulation of the CDC20 substrate p21, prolonging mitotic exit. These activities also occurred with a CYP24A1 isoform 2 lacking the catalytic cysteine (Cys-462), suggesting that CYP24A1's oncogenic potential is independent of its catalytic activity. CYP24A1 degradation reduced clonogenic survival of mutant KRAS-driven lung cancer cells, and calcitriol treatment increased CYP24A1 levels and tumor burden in Lsl-KRASG12D mice. These results disclose a catalytic activity-independent growth-promoting role of CYP24A1 in mutant KRAS-driven lung cancer. This suggests that CYP24A1 could be therapeutically targeted in lung cancers in which its expression is high.




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ABC transporters control ATP release through cholesterol-dependent volume-regulated anion channel activity [Signal Transduction]

Purinergic signaling by extracellular ATP regulates a variety of cellular events and is implicated in both normal physiology and pathophysiology. Several molecules have been associated with the release of ATP and other small molecules, but their precise contributions have been difficult to assess because of their complexity and heterogeneity. Here, we report on the results of a gain-of-function screen for modulators of hypotonicity-induced ATP release using HEK-293 cells and murine cerebellar granule neurons, along with bioluminescence, calcium FLIPR, and short hairpin RNA–based gene-silencing assays. This screen utilized the most extensive genome-wide ORF collection to date, covering 90% of human, nonredundant, protein-encoding genes. We identified two ABCG1 (ABC subfamily G member 1) variants, which regulate cellular cholesterol, as modulators of hypotonicity-induced ATP release. We found that cholesterol levels control volume-regulated anion channel–dependent ATP release. These findings reveal novel mechanisms for the regulation of ATP release and volume-regulated anion channel activity and provide critical links among cellular status, cholesterol, and purinergic signaling.




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Inflammatory and mitogenic signals drive interleukin 23 subunit alpha (IL23A) secretion independent of IL12B in intestinal epithelial cells [Signal Transduction]

The heterodimeric cytokine interleukin-23 (IL-23 or IL23A/IL12B) is produced by dendritic cells and macrophages and promotes the proinflammatory and regenerative activities of T helper 17 (Th17) and innate lymphoid cells. A recent study has reported that IL-23 is also secreted by lung adenoma cells and generates an inflammatory and immune-suppressed stroma. Here, we observed that proinflammatory tumor necrosis factor (TNF)/NF-κB and mitogen-activated protein kinase (MAPK) signaling strongly induce IL23A expression in intestinal epithelial cells. Moreover, we identified a strong crosstalk between the NF-κB and MAPK/ERK kinase (MEK) pathways, involving the formation of a transcriptional enhancer complex consisting of proto-oncogene c-Jun (c-Jun), RELA proto-oncogene NF-κB subunit (RelA), RUNX family transcription factor 1 (RUNX1), and RUNX3. Collectively, these proteins induced IL23A secretion, confirmed by immunoprecipitation of endogenous IL23A from activated human colorectal cancer (CRC) cell culture supernatants. Interestingly, IL23A was likely secreted in a noncanonical form, as it was not detected by an ELISA specific for heterodimeric IL-23 likely because IL12B expression is absent in CRC cells. Given recent evidence that IL23A promotes tumor formation, we evaluated the efficacy of MAPK/NF-κB inhibitors in attenuating IL23A expression and found that the MEK inhibitor trametinib and BAY 11–7082 (an IKKα/IκB inhibitor) effectively inhibited IL23A in a subset of human CRC lines with mutant KRAS or BRAFV600E mutations. Together, these results indicate that proinflammatory and mitogenic signals dynamically regulate IL23A in epithelial cells. They further reveal its secretion in a noncanonical form independent of IL12B and that small-molecule inhibitors can attenuate IL23A secretion.




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Can the UK Strike a Balance Between Openness and Control?

2 March 2020

Hans Kundnani

Senior Research Fellow, Europe Programme
Rather than fetishizing free trade, Britain should aim to be a model for a wider recalibration of sustainable globalization.

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Boris Johnson speaks at the Old Naval College in Greenwich on 3 February. Photo: Getty Images.

This week the UK will start negotiating its future relationship with the European Union. The government is trying to convince the EU that it is serious about its red lines and is prepared to walk away from negotiations if the UK’s ‘regulatory freedom’ is not accepted – a no-deal scenario that would result in tariffs between the EU and the UK. Yet at the same time the story it is telling the world is that Britain is ‘re-emerging after decades of hibernation as a campaigner for global free trade’, as Boris Johnson put it in his speech in Greenwich a few weeks ago.

The EU is understandably confused. It’s a bit odd to claim to be campaigning for free trade at the exact moment you are creating new barriers to trade. If Britain were so committed to frictionless trade, it wouldn’t have left the EU in the first place – and having decided to leave, it would have sought to maintain a close economic relationship with the EU, like that of Norway, rather than seek a basic trade deal like Canada’s. 

As well as creating confusion, the narrative also absurdly idealizes free trade. Johnson invoked Richard Cobden and the idea that free trade is ‘God’s diplomacy – the only certain way of uniting people in the bonds of peace since the more freely goods cross borders the less likely it is that troops will ever cross borders’. But the idea that free trade prevents war was shattered by the outbreak of the First World War, which brought to an end the first era of globalization.

We also know that the domestic effects of free trade are more complex and problematic than Johnson suggested. Economic liberalization increases efficiency by removing friction but also creates disruption and has huge distributional consequences – that is, it creates winners and losers. In a democracy, these consequences need to be mitigated.

In any case, the world today is not the same as the one in which Cobden lived. Tariffs are at a historically low level – and many non-tariff barriers have also been removed. In other words, most of the possible gains from trade liberalization have already been realized. Johnson talked about the dangers of a new wave of protectionism. But as the economist Dani Rodrik has argued, the big problem in the global economy is no longer a lack of openness, it is a lack of democratic legitimacy.

The UK should therefore abandon this confusing and misleading narrative and own the way it is actually creating new barriers to trade – and do a better job of explaining the legitimate reasons for doing so. Instead of simplistically talking up free trade, we should be talking about the need to balance openness and economic efficiency with democracy and a sense of control, which is ultimately what Brexit was all about. Instead of claiming to be a ‘catalyst for free trade’, as Johnson put it, the UK should be talking about how it is trying to recalibrate globalization and, in doing so, make it sustainable.

In the three decades after the end of the Cold War, globalization got out of control as barriers to the movement of capital and goods were progressively removed – what Rodrik called ‘hyper-globalization’ to distinguish it from the earlier, more moderate phase of globalization. This kind of deep integration necessitated the development of a system of rules, which have constrained the ability of states to pursue the kind of economic policy, particularly industrial policy, they want, and therefore undermined democracy.

Hyper-globalization created a sense that ‘the nation state has fundamentally lost control of its destiny, surrendering to anonymous global forces’, as the economist Barry Eichengreen put it. Throughout the West, countries are all struggling with the same dilemma – how to reconcile openness and deep integration on the one hand, and democracy, sovereignty and a sense of control on the other.

Within the EU, however, economic integration and the abolition of barriers to the movement of capital and goods went further than in the rest of the world – and the evolution of the principle of freedom of movement after the Maastricht Treaty meant that barriers to the internal movement of people were also eliminated as the EU was enlarged. What happened within the EU might be thought of as ‘hyper-regionalization’ – an extreme example, in a regional context, of a global trend.

EU member states have lost control to an even greater extent than other nation states – albeit to anonymous regional rather than global forces – and this loss of control was felt intensely within the EU. It is therefore logical that this led to an increase in Euroscepticism. Whereas the left wants to restore some barriers to the movement of capital and goods, the right wants to restore barriers to the movement of people.

However, having left the EU, the UK is uniquely well placed to find a new equilibrium. The UK has an ideological commitment to free trade that goes back to the movement to abolish the Corn Laws in the 1840s – which Johnson’s speech expressed. It is difficult to imagine the UK becoming protectionist in any meaningful sense. But at the same time, it has a well-developed sense of national and popular sovereignty, and the sense that the two go together – which is why it was so sensitive to the erosion of them through the EU. This means that Britain is unlikely to go to one extreme or the other.

In other words, the UK may be the ideal country to find a new balance between openness and integration on the one hand, and a sense of control on the other. If it can find this balance – if it can make Brexit work – the UK could be a model for a wider recalibration of sustainable globalization. That, rather than fetishizing free trade, is the real contribution the UK can make.

A version of this article was originally published in the Observer.