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Antiviral Properties and Mechanism of Action Studies of the Hepatitis B Virus Capsid Assembly Modulator JNJ-56136379 [Antiviral Agents]

By aac.asm.org
Published On :: 2020-04-21T08:01:10-07:00

Capsid assembly is a critical step in the hepatitis B virus (HBV) life cycle, mediated by the core protein. Core is a potential target for new antiviral therapies, the capsid assembly modulators (CAMs). JNJ-56136379 (JNJ-6379) is a novel and potent CAM currently in phase II trials. We evaluated the mechanisms of action (MOAs) and antiviral properties of JNJ-6379 in vitro. Size exclusion chromatography and electron microscopy studies demonstrated that JNJ-6379 induced the formation of morphologically intact viral capsids devoid of genomic material (primary MOA). JNJ-6379 accelerated the rate and extent of HBV capsid assembly in vitro. JNJ-6379 specifically and potently inhibited HBV replication; its median 50% effective concentration (EC50) was 54 nM (HepG2.117 cells). In HBV-infected primary human hepatocytes (PHHs), JNJ-6379, when added with the viral inoculum, dose-dependently reduced extracellular HBV DNA levels (median EC50 of 93 nM) and prevented covalently closed circular DNA (cccDNA) formation, leading to a dose-dependent reduction of intracellular HBV RNA levels (median EC50 of 876 nM) and reduced antigen levels (secondary MOA). Adding JNJ-6379 to PHHs 4 or 5 days postinfection reduced extracellular HBV DNA and did not prevent cccDNA formation. Time-of-addition PHH studies revealed that JNJ-6379 most likely interfered with postentry processes. Collectively, these data demonstrate that JNJ-6379 has dual MOAs in the early and late steps of the HBV life cycle, which is different from the MOA of nucleos(t)ide analogues. JNJ-6379 is in development for chronic hepatitis B treatment and may translate into higher HBV functional cure rates.


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Washington Capitals investigating Brendan Leipsic's 'unacceptable and offensive comments'

By www.winnipegfreepress.com
Published On :: Thu, 7 May 2020 09:33:42 CDT

Screenshots showing repugnant and insulting remarks — some misogynistic, some racist, others hinting at drug use and sexual conquests — from a private group chat between several hockey players, including ...


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Capitals to terminate Brendan Leipsic's contract following fallout from leaked messages

By feeds.foxnews.com
Published On :: Fri, 08 May 2020 17:00:08 GMT

The Washington Capitals announced Friday that forward Brendan Leipsic was placed on unconditional waivers after his private messages were leaked on social media Wednesday.


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Outlook: Nifty upside capped; stay defensive, protect profits

By economictimes.indiatimes.com
Published On :: 2020-05-09T15:26:21+05:30

The upside potential will remain capped, and the index will turn vulnerable again.


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Everything You Need to Make a Campsite at Home--Indoors or Out!

By www.eonline.com
Published On :: Fri, 08 May 2020 21:42:00 GMT

We love these products, and we hope you do too. E! has affiliate relationships, so we may get a small share of the revenue from your purchases. Items are sold by the retailer, not...


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Capitals forward Brendan Leipsic apologizes after 'inappropriate and offensive' comments go public

By www.cbc.ca
Published On :: Wed, 6 May 2020 20:20:05 EDT

Washington Capitals forward Brendan Leipsic suddenly finds himself in hot water. A private group chat featuring Leipsic was leaked on Wednesday, including misogynistic comments made by the NHLer.


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  • Sports/Hockey/NHL
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Capitals waive Brendan Leipsic after misogynistic comments made public

By www.cbc.ca
Published On :: Fri, 8 May 2020 11:19:34 EDT

The Washington Capitals placed Brendan Leipsic on unconditional waivers on Friday, two days after it was revealed the forward made misogynistic comments in a private group chat. The team said the move was made with the intention of terminating Leipsic's contract.


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  • Sports/Hockey/NHL
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Winnipeg-born Brendan Leipsic’s comments ‘unacceptable and offensive’: NHL

By globalnews.ca
Published On :: Thu, 07 May 2020 02:09:42 +0000

Winnipeg-born NHL player Brendan Leipsic is facing massive criticism after private messages degrading women were exposed online.


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Winnipeg-born NHL player Brendan Leipsic’s contract terminated by Washington Capitals

By globalnews.ca
Published On :: Fri, 08 May 2020 15:59:48 +0000

The Washington Capitals announced in a statement Friday morning that Brendan Leipsic has been placed on unconditional waivers for the purposes of terminating his contract.


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Covid-19 competence has given Australian governments some political capital. But there's a flipside | Katharine Murphy

By www.theguardian.com
Published On :: 2020-05-08T20:00:36Z

Politicians have set a high bar for themselves – success on coronavirus has created community expectations that will be challenging to shift

“Let’s not give everything back, let’s not throw away all the progress we’ve made by letting our frustration get the better of us.” This was Daniel Andrews on Friday afternoon, shortly after national cabinet resolved to gradually restart economic and social activity by July.

The Victorian premier wanted people to understand he’d be hastening slowly – the message being here in the Massachusetts of Australia, we decide how quickly we’ll remove coronavirus restrictions. We don’t apply an arbitrary national average.

Continue reading...


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Everything You Need to Make a Campsite at Home--Indoors or Out!

By www.eonline.com
Published On :: Fri, 08 May 2020 21:42:00 GMT

We love these products, and we hope you do too. E! has affiliate relationships, so we may get a small share of the revenue from your purchases. Items are sold by the retailer, not...


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Dave Feschuk: The Brendan Leipsic misogynistic group chat is a form of violence that leaves scars

By www.thestar.com
Published On :: Thu, 7 May 2020 20:57:08 EDT


There’s a culture around the way men at their worst treat women, Dave Feschuk writes. It’s not just a problem in sports, but in society, and it requires attention.


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Capitals cut ties with Brendan Leipsic after leak of disparaging and misogynistic social media comments

By www.thestar.com
Published On :: Fri, 8 May 2020 12:49:00 EDT


The former Leafs forward commented on the physical appearances of Vancouver forward Tanner Pearson’s wife and Edmonton captain Connor McDavid’s girlfriend. He also called Capitals linemates Garnet Hathaway and Nick Dowd losers.


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Superannuation early withdrawal risks collapsing retirement system

By www.abc.net.au
Published On :: Tue, 28 Apr 2020 15:52:29 +1000

Super funds and prominent professional investors warn that the mass withdrawal of funds from superannuation during the COVID-19 crisis risks undermining the whole retirement income system.


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In the blink of an eye coronavirus has turned the property market upside down

By www.abc.net.au
Published On :: Mon, 04 May 2020 06:13:44 +1000

Within the space of a month, the coronavirus pandemic has upended the property market for buyers, sellers, tenants and landlords.


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Cas Brendan Leipsic: Cinq autres sportifs coulés par les réseaux sociaux

By www.journaldemontreal.com
Published On :: Sat, 09 May 2020 10:41:34 EDT

Certaines opinions exprimées sur les réseaux sociaux viennent parfois jouer de vilains tours.


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Everything You Need to Make a Campsite at Home--Indoors or Out!

By www.eonline.com
Published On :: Fri, 08 May 2020 21:42:00 GMT

We love these products, and we hope you do too. E! has affiliate relationships, so we may get a small share of the revenue from your purchases. Items are sold by the retailer, not...


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Justice Department Sues Ypsilanti, Mich., Landlords for Sexual Harassment

By www.justice.gov
Published On :: Thu, 29 Jan 2009 13:22:37 EST

The Department today filed suit against Ronald D. Peterson and Glen E. Johnson, the owner and rental manager, respectively, of 11 single family homes in Ypsilanti, Mich., alleging a pattern or practice of sexual harassment of female tenants.


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  • OPA Press Releases
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Gasdermin D inhibitor protects against sepsis

By feeds.nature.com
Published On :: 2020-05-08


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Fetal inheritance of chromosomally integrated human herpesvirus 6 predisposes the mother to pre-eclampsia

By feeds.nature.com
Published On :: 2020-05-04


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Author Correction: Vitamin lipid nanoparticles enable adoptive macrophage transfer for the treatment of multidrug-resistant bacterial sepsis

By feeds.nature.com
Published On :: 2020-04-28


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Multifunctional opsins

By feeds.nature.com
Published On :: 2020-04-23


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Collapsible Candidates from Iowa to New Hampshire

By webfeeds.brookings.edu
Published On :: Wed, 09 Jan 2008 12:00:00 -0500

After his first place finish in Iowa, which was supposed to propel him to a New Hampshire victory, “change” is probably a word Barack Obama does not like as much anymore. But, his support did not really change much between these two elections. He won 38 percent of Iowa’s delegates and 36 percent of New Hampshire’s vote. It was Hillary Clinton and John McCain who were the big change candidates.

What happens when a presidential candidate that does well in a primary or caucus state, does not do so well in the next? The dynamic of the presidential election can swiftly and stunningly change, as it did in New Hampshire on Tuesday.

How Barack Obama wishes John Edwards showed up in New Hampshire.

Edwards was awarded 30 percent of Iowa’s delegates, barely denying Clinton a second place finish. He finished a distant third in New Hampshire, receiving only 17 percent of the vote. There are strong indications that a shift among his supporters helped propel Hillary Clinton to her New Hampshire victory.

According to the exit polls, Edwards did 8 percentage points worse in New Hampshire among women, while Clinton did 16 percent better. Obama’s support was virtually identical, dropping a statistically insignificant 1 percentage point.

Obama’s support among young people remained strong, if slightly increasing among 18-24 and 30-39 year olds. Clinton’s support remained strong and slightly increased among those 65 and older. Edwards won Iowa’s middle-aged voters, age 40-64, but it was Clinton who decisively won this coveted age demographic in New Hampshire. And where these people were 38 percent Iowa caucus attendees, they were 54 percent of New Hampshire voters. (To understand why their turnout increased, see my analysis of Iowa’s turnout .)

Moving forward, the generational war is still a strong dynamic in the Democratic race, as evident in the candidates’ speech styles following the election results. In Iowa, Clinton was flanked by the ghosts of the Clinton administration. In New Hampshire, she shared the stage with a sea of young voters. In Iowa, Obama spoke of change, a message that resonates with younger people who are not part of the establishment. In New Hampshire his slogan was a message that echoes the can-do spirit of the greatest generation, “Yes, we can!”

In the days between Iowa and New Hampshire, Edwards spoke about how he wanted the election to become a two-way race. One should be careful with what one wishes for. Edwards and Clinton are vying for the same support base, that when united can defeat Obama, at least in New Hampshire. In the short-term, Obama most needs Edwards to do better so that support can continue to be divided.

Among Republicans, John McCain recreated his magic of eight years ago and bounced back strong from a poor Iowa showing to win New Hampshire.

The Iowa and New Hampshire electorates are so different it is difficult to compare them. In Iowa, Evangelical Christians were 60 percent of the electorate, while in New Hampshire, they were only 23 percent. Mike Huckabee’s move from first in Iowa to third in New Hampshire can be clearly attributed to the shrinking of his base. His collapse paved the way for a new winner to emerge.

It is thus tempting to attribute McCain’s victory solely to the different electorates, but he still had to defeat Mitt Romney to win New Hampshire.

According to the exit polls, the battle between McCain and Romney is a referendum on the Bush administration. Surprisingly, McCain, who has tried to rebuild bridges with the Bush establishment since his defeat in the 2000 presidential election, is still seen as the outsider and agent of change by voters participating in the Republican nomination process.

In both Iowa and New Hampshire, McCain drew his support from those who said they are angry or dissatisfied with the Bush administration. Romney drew his support from those who said they are enthusiastic or satisfied. Not surprisingly, McCain is also drawing more support from self-described Independents and Romney from Republicans.

The candidates seem to understand this dynamic, too, as they gave their speeches following the election results. In a contrived bit of acting, Romney showed up on stage without a podium and shoved a prepared speech back into his pocket (if he had needed a podium, his advance team would have provided it). He appeared relaxed, delivering his speech in a personable style reminiscent of Huckabee, who is competing with Romney for those who support Bush. But he also seemed to be reaching out to Independents with a message of change. In stark contrast, McCain delivered a carefully written, almost sedate speech designed to reassure Republicans of his conservative credentials.

This three-way dynamic between Huckabee, McCain, and Romney should prove fascinating as the Republican nomination process moves forward. Where Evangelicals are strong, Huckabee should do well. Where they are not, the rules governing if Independents can or cannot participate will dictate how McCain and Romney do. And we have yet to see regional candidates like Fred Thompson have their day in the sun. And then there is Rudy Giuliani, who is lying in wait in the larger states where his name recognition should give him a significant boost over the other candidates. All of this points to an extended campaign among Republicans.

Michael P. McDonald is an Associate Professor at George Mason University and a Non-Resident Senior Fellow at the Brookings Institution. He studies voter turnout and is a consultant to the national exit poll organization.

     
 
 


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Presidential Campaign Update: Al & Arnold At The New Hampsire Primary

By www.treehugger.com
Published On :: Sat, 17 Nov 2007 10:00:26 -0500

This is wonderful. A bi-partisan political storm is brewing over New Hampshire because Al and Arnold have found a clever way to inject serious climate discussion into the coming US presidential primary season. Timing could not be better, with the IPCC


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Stash this collapsible water bottle in your pocket and turn back to the tap

By www.treehugger.com
Published On :: Fri, 01 Aug 2014 13:51:48 -0400

It's time we made water bottles part of our every day carry (EDC) kit. This handy little bottle squishes down small enough to go everywhere you do.


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These 100 popsicles are made with trash- and sewage-filled water

By www.treehugger.com
Published On :: Tue, 13 Jun 2017 16:09:18 -0400

The Polluted Water Popsicles project is meant to shock viewers into realizing how serious water contamination is in Taiwan.


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Solar Still Makes Water Purification Easy, Works Like an Upside-Down Coffee Maker

By www.treehugger.com
Published On :: Wed, 26 Oct 2011 11:19:06 -0400

This simple, innovative solar still purifies water without electricity or filters.


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Portable, collapsible wind turbine weighs less than 4 pounds

By www.treehugger.com
Published On :: Wed, 14 May 2014 07:00:00 -0400

The WindPax wind generator fits neatly into a backpack for hiking or can be used in the backyard too.


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The surprising upside to childhood thumb-sucking and nail-biting

By www.treehugger.com
Published On :: Mon, 11 Jul 2016 12:35:34 -0400

Grimy fingers in the mouth leads to decreased risk of developing allergies, new study suggests.


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Fashionistas Chill Out at Pepsi®'s Glam Lounge During Fashion Forward Dubai - Pepsi at Dubai Fashion Forward 2016

By feedproxy.google.com
Published On :: 26 Apr 2016 14:40:00 EDT

Pepsi at Dubai Fashion Forward 2016


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Fashionistas Chill Out at Pepsi®'s Glam Lounge During Fashion Forward Dubai - Pepsi at Dubai Fashion Forward 2016

By feedproxy.google.com
Published On :: 26 Apr 2016 14:40:00 EDT

Pepsi at Dubai Fashion Forward 2016


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Trade groups representing PepsiCo, Procter & Gamble and others want guidance on factories from Pence

By www.cnbc.com
Published On :: Thu, 07 May 2020 16:30:09 GMT

Trade groups representing the country's biggest consumer companies, including PepsiCo, Procter & Gamble and Clorox, wrote a letter to Vice President Mike Pence on Thursday urging federal guidance on how to safely manage their factory workers as states begin to reopen for business.


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Brazil finish top of Group D after lopsided win

By www.fifa.com
Published On :: Tue, 26 Nov 2019 17:41:00 GMT


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PSI helps locate cabbie lying paralysed on Navi Mumbai highway

By www.mid-day.com
Published On :: 10 Apr 2019 01:20:05 GMT

The efforts of a persistent police officer and the victim's brother saved the life of a 36-year-old taxi driver, Madan Paswan, who had suffered a paralysis attack and was lying helpless in his taxi on the highway in Navi Mumbai.

The incident happened on the morning of March 23, around 10 am, when Paswan's younger brother Ishwar received a call from the former's wife from his hometown in Koderma district of Jharkhand. "Soon after getting the paralysis attack, he [Paswan] called his wife in Koderma, but fumbled during the conversation and then disconnected the phone. His wife got worried and called me," Ishwar said.

Ishwar said he then called Paswan who accepted his call but did not say anything on the phone. Worried, Ishwar called his friends and relatives who started searching for Paswan in the city. Paswan lives in Shastri Nagar, Vile Parle East, so Ishwar rushed to the Vile Parle police station and informed sub-inspector Sachin Chavan about the situation. Chavan, too, called Paswan, but no one spoke at the other end.

Also Read: Mumbai: Off-duty female PSI, DCP save accident victims from bleeding to death


Ishwar (left) gathered his friends and family to search for his brother Madan; the senior officers are considering a reward for PSI Sachin Chavan (right) for saving Madan Paswan's life

"There was definitely something amiss," Chavan said, adding that he immediately sought help from the office of the zonal deputy commissioner of police to track his location via his phone. Meanwhile, Chavan told Ishwar to visit the Sion police station as Paswan takes the taxi on rent from there. As he couldn't get any information here, he went back to Vile Parle police station around 11.30 am and then left to join his friends and family in searching for Paswan. Chavan, who was coordinating with Ishwar on the phone, gave him Paswan's exact location -- Sanpada in Navi Mumbai.

They rushed to the location around 3 pm and found Paswan "lying inside the taxi almost unconscious. We shook his hands and legs but he was unable to speak. We rushed him to JJ Hospital," said Ishwar. "Paswan had got a paralysis attack when he was driving his taxi on the highway. Many motorists passed his taxi but no one bothered to check why it was parked on a busy highway," Chavan said.

Also Read: Mumbai: One rescued, two stuck after falling inside septic tank in Chembur

Paswan had met with an accident in 2004 in Ghaziabad. He had suffered serious head injuries in the accident. The family suspects the paralysis attack was a result of this injury as Paswan had complained of acute headaches recently. Paswan left for Koderma after being discharged from JJ Hospital. He is currently not in a condition to speak, his family members said. Meanwhile, senior police officers are considering to reward Chavan for his prompt action that saved Paswan's life.

Also Read: Labourer's son, cabbie's daughter picked for QPR training

Catch up on all the latest Crime, National, International and Hatke news here. Also download the new mid-day Android and iOS apps to get latest updates



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New AI Model Could Aid Brain Cancer Patients Avoid Biopsies

By www.medindia.net
Published On ::

Brain cancer patients typically need a biopsy so physicians can assess their mutation status and make a treatment decision. But, a new AI (Artificial


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Reliability of Biopsies from Donated Kidneys Prior to Transplantation Examined

By www.medindia.net
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A new study published in CJASN indicated that biopsies of donated kidneys are likely not useful for assessing organ quality prior to transplantation unless


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Genetic Signature may Recognize Mothers at Risk for Preeclampsia

By www.medindia.net
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New genetic signature combining specific maternal and fetal gene variants are associated with a higher risk of preeclampsia, reports a new study. The


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Protein Produced in Sepsis Helps Lower Blood Pressure

By www.medindia.net
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In mice, halting the activity of c-Jun N-terminal kinase (JNK) and B-type natriuretic peptide (BNP) protein was found to reverse cardiovascular damage


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Sepsis a Leading Cause of Death in US Hospitals

By www.medindia.net
Published On ::

Even though many attempts are being made for better detection and treatment of sepsis, their role in many associated deaths and their prevention remains unknown.


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Mother's Milk may Protect Premature Babies from Sepsis

By www.medindia.net
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Breastfeeding can protect preemies from developing deadly infections such as sepsis, reports a new study. The findings of the study are published in the


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Mindfulness Meditation Enhances Positive Effects of Psilocybin: Study

By feedproxy.google.com
Published On ::

Mindfulness meditation was found to enhance the positive long-term effects of a single dose of psilocybin, which is found in certain mushrooms, revealed University of Zurich researchers.


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Epsilon, Leader in Customer Loyalty Solutions for Large Organizations

By feedproxy.google.com
Published On ::

Epsilon, the global leader in creating connections between people and brands, today announced that it was named a Leader in the January 2016 report �The Forrester Wave�: Customer Loyalty Solutions For Large Organizations.


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Portugal Stock Market (PSI20)

By tradingeconomics.com
Published On :: Sat, 09 May 2020 14:45:00 GMT

The PSI 20 decreased 1027 points or 19.51% since the beginning of 2020, according to trading on a contract for difference (CFD) that tracks this benchmark index from Portugal. Historically, the Portugal Stock Market (PSI20) reached an all time high of 15080.99 in March of 2000. The Portuguese Stock Index PSI 20 is a benchmark stock market index which tracks the performance of 20 companies with the largest market capitalization and share turnover in the Euronext Lisbon Stock Exchange. It is a free-float, capitalization weighted index. The PSI 20 Index has a base value of 3000 as of December 31, 1992.


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Panama Stock Market (BVPSI)

By tradingeconomics.com
Published On :: Sat, 09 May 2020 14:45:00 GMT

The BVPSI decreased 66 points or 14.57% since the beginning of 2020, according to trading on a contract for difference (CFD) that tracks this benchmark index from Panama. Historically, the Panama Stock Market (BVPSI) reached an all time high of 490.09 in May of 2018. The Panama Stock Exchange BVPSI Index is a major stock market index which tracks the performance of the biggest companies listed on the Panama Stock Exchange. The BVPSI Index has a base value of 100 as of December 3 1, 2002.


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PepsiCo’s food and drink combo serves it well in lockdown snacking surge

By www.ft.com
Published On :: Tue, 28 Apr 2020 15:14:53 GMT

Sales rise but company warns revenues will decline as bar and restaurant closures hit beverages


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The world economy is now collapsing

By www.ft.com
Published On :: Tue, 14 Apr 2020 15:36:21 GMT

A microbe has overthrown our arrogance and sent global output into a tailspin


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Qatar World Cup officials ask Glastonbury Festival organisers to help design campsites for fans

By www.dailymail.co.uk
Published On :: Mon, 23 Dec 2019 21:02:53 GMT

Qatar World Cup officials have asked Glastonbury Festival organisers to help them plan desert camp sites for fans ahead of the 2022 tournament, according to The Mirror.


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More homeless migrants arrive at Park Lane campsite and leave Hyde Park littered with rubbish

By www.dailymail.co.uk
Published On :: Mon, 30 Sep 2019 12:07:48 GMT

A dozen tents housing around 20 rough sleepers have been set up on Park Lane, across the road from the London Hilton hotel and the area is strewn with litter, empty food cartons and drug paraphernalia.


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