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The crucial p53-dependent oncogenic role of JAB1 in osteosarcoma in vivo





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Using Bezier Curve analysis in context of Expression Analysis

Modeste, Previste Using Bezier Curve analysis in context of Expression Analysis., 2019 . In ICASSP. (In Press) [Conference paper]




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American companies spent years in an economic boom. Then the coronavirus hit

The pandemic could cast a long shadow, permanently changing how companies spend money, sell goods and run their businesses.




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No ‘Silence, s’il vous plaît’? French Open could take place without fans

The French Open tennis tournament at Roland Garros could be held without fans later this year, the president of the French Tennis Federation (FTF) said on Sunday.




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Covid-19: Europe begins easing lockdown measures

Tentatively, parts of Europe are emerging from lockdown, with France and Belgium joining the list of countries easing measures on Monday, amid fears of a second coronavirus wave.




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France holds its breath on the eve of Covid-19 lockdown lifting

As France begins to lift its eight-week Covid-19 lockdown, the government is stepping up efforts to ‘protect, test and isolate’. But many still fear a second wave.  




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Brighton cite 'concerns' over restart as third player tests positive for Covid-19

  • Unnamed player to go into 14-day isolation
  • Chief executive: every club is sizing up restart with self-interest

A third Brighton and Hove Albion player has tested positive for coronavirus, the club’s chief executive has said.

Related: Using players as guinea pigs would wipe out Premier League's integrity | Paul Wilson

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Using players as guinea pigs would wipe out Premier League's integrity | Paul Wilson

The final league table will merit the biggest asterisk in history if teams are full of footballers who don’t want to be on the pitch

Anyone who has spent the best part of an hour just waiting to cross a supermarket threshold in the past few weeks will be aware how quickly the outlandish becomes the new normal. Yet even in these strange days it was still odd to hear Gordon Taylor pop up on the radio with the suggestion that shortened games might be the solution to finishing the Premier League season sometime before the clocks go back.

How that would have helped maintain the integrity of the competition or assisted those clubs worried they might be relegated in less than optimum circumstances remained unclear, for the Premier League was pooh-poohing the idea proposed by the Professional Footballers’ Association’s leader as ridiculous and unfounded within hours.

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La Liga players test positive with five new cases confirmed in top two leagues

  • Real Sociedad goalkeeper Remiro confirms positive
  • La Liga plans to return without spectators in June

Five players in Spain’s top two divisions have tested positive for Covid-19 since clubs began testing players and staff members last week, with the Real Sociedad goalkeeper Álex Remiro confirming himself as one of the cases.

A statement from La Liga said the players would remain at home where they would continue individual training before being tested again “in the next few days” to determine whether they can return to their club’s training ground.

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Bundesliga CEO adamant season will restart despite positive tests at Dresden

  • Dresden players sent home after two test positive
  • ‘We are not changing our plans,’ says Christian Seifert

The Bundesliga is keen to press ahead with plans to restart the season for the top two tiers next weekend, despite Dynamo Dresden’s squad being quarantined for two weeks.

Dresden’s players were sent home after two tested positive for coronavirus. This means the second tier club cannot play their first two games of the restart – against Hannover on 17 May and against Fürth the following weekend.

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Nathan Redmond: 'It's difficult to post a TikTok video if you've lost 1-0' | David Hytner

The Covid-19 lockdown has given the midfielder the chance to show his acting skills outside the Southampton changing room

Nathan Redmond hustles towards the camera, suited up, fedora jauntily perched and when he starts to lip-sync, the voice is that of Carter – the character played by Chris Tucker in Rush Hour 3. It is the scene involving him, Master Yu and Mi and, for those who have not seen it, has Carter getting into a word-play tangle as he questions Yu and Mi. “Who are you? Yu. No, not me, you. Yes, I am Yu.” It goes from there.

Related: 'People's lives depend on it': the sacked English defender left in limbo | Sid Lowe

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Global report: Covid-19 cases rise in Germany as Wuhan reports first infection in weeks

Global infections surpass 4m; cluster detected in Dordogne, new cases highlight risks as lockdowns eased

New coronavirus infections rose again in Germany at the end of last week, a few days after leaders loosened social restrictions, while the Chinese city of Wuhan announced it had detected its first case in weeks, helping to push the global total past 4m on Sunday.

On the eve of the UK starting to ease its lockdown on Monday, the new cases in Germany and China illustrated the difficulties governments will face over the next months as they attempt to reopen their societies without triggering a second wave of infections.

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'People feel a bit nervous': France braces for end of lockdown

As schools and businesses get set to reopen some citizens urge caution, wary of a spike in infections

France is set to end eight weeks of strict lockdown as the government urged people to behave responsibly to avoid a sudden spike in coronavirus cases.

Hours before the national déconfinement there were reports of two new Covid-19 clusters in départments designated green – areas where the virus has largely stopped circulating and where most restrictions are being lifted.

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Lockdown diary: 'There's a gran isolating in a tree communicating by catapult!'

Like man buns on scooters and ukulele busking, Covid-19 has now spread to the north from London – inspiring a coronavirus soapcom from our self-isolating comedy-writer

Up here in the north-west, we’re used to living in the slipstream of London’s sleek urban shenanigans. Whatever the cultural breakthrough – man buns on scooters, cashless ukulele busking, emotional support bees – it takes a while to reach the Lancaster and Morecambe Non-Metropolitan Area. If it ever does.

A Street Stranger Watch leads to a death and the appearance at midnight of the street’s original Victorian inhabitants

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William Smethurst obituary

Radio and TV producer who revitalised The Archers during his tenure as editor

Despite being a soft-spoken Lancastrian of mild-mannered appearance, the writer and producer William Smethurst, who has died aged 71, was known to his detractors in radio and television as “Butcher Bill”. But the ruthless skills combined with mischievous flair that he displayed as editor of The Archers for eight years from 1978 were widely credited with saving Radio 4’s flagging rural soap opera and making it the cult show it later became. Smethurst was the man who licensed writers to scandalise sleepy Ambridge and once persuaded Princess Margaret to make a guest appearance.

He was less successful when Central TV lured him from BBC Pebble Mill in Birmingham to pull off the same trick with Crossroads, its Midlands motel saga, which had run out of steam. Smethurst ditched Tony Hatch’s theme tune, killed off characters (much as he had Dan and Doris Archer), and made the plots (and scenery) more credible and the cast much more glamorous, with the help of the motel swimming pool he installed. Some critics preferred its previous awfulness and the show folded in 1988.

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Race relations in 2016: much to deplore but plenty to applaud

No one should be complacent about racism but the story is rarely as straightforward as some commentators routinely assert

In my city neighbourhood this summer a man on the run from police custody hit a black woman in the face. Understandably, she reported it as a racial attack. Except it probably wasn’t. The runaway also hit a boy when his mother opened the door and tried to spray another woman’s hair red at a bus stop. He had mental health problems.

Not much harm done in this instance. But it’s one reason why I don’t often write about race relations in modern Britain, though I first did so 50 years ago when many aspects of them were pretty grim.

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EU referendum two months on: the 10 steps that led to Brexit

As the dust settles, hindsight makes the chain of events that culminated in UK’s vote to leave easier to discern

It is two months since British voters surprised themselves by deciding to end the UK’s 43-year relationship with the European Union – “independence day” to some and “the worst political decision since 1945” to others.

As stunned political leaderships on both sides of the Channel continue dithering about what to do next, it is worth looking back at the origins of a crisis the EU elite had not expected.

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Who lives at No 9 Downing Street?

The anatomy of Downing Street is complicated. The prime minister doesn’t live at No 10, No 9 has become a power address since the Brexit vote, and then there’s the house at the end …

No 9: That’s the boring property next to the security gates on the west side of Whitehall, the one that TV news crews never bother to film because it leads a quiet life. All this may change now that it is set to become Brexit HQ, David Davis’s centre of Leave EU planning, or possibly of panic, plots and pique. No 9 used to be the office of the judicial committee of the privy council until that moved into the old Middlesex Guildhall along with the new-fangled supreme court in 2009. In recent years, it has been the office of the chief whip, though their official address remains No 12. But Davis, an old Whitehall hand, refused to be fobbed off with a base so far from Theresa May that it was almost in Wales. He has what he wants: his officials have a power address.

Related: Boris Johnson forced to share mansion with Liam Fox and David Davis

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Owen Smith may not beat Jeremy Corbyn, but he passed the Today test | Michael White

As he tussled with John Humphrys on Radio 4, the Labour leadership challenger sounded confident, articulate and human

Listening to the radio this morning I had an experience I realised I’d almost forgotten. It was the sound of a Labour politician being combatively quizzed on Radio 4 by Today’s John Humphrys in the key 8.10 spot and giving confident, articulate answers in return. When did I last hear that, I wondered?

What follows here isn’t a party political broadcast for Owen Smith. For the first time since Labour’s glittering leadership contest to succeed Harold Wilson in 1976 – Callaghan versus Healey, Foot, Crosland, Jenkins and Benn – he’s a leadership contender whom OAP Mike doesn’t really know.

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Resentful Americans turn a blind eye to Trump's faults

The candidate’s excesses appeal to voters who feel marginalised and for whom the temptation is to blur reality and illusion

Whenever I think about the dysfunctional horror of the looming presidential election in America – so weird that Nigel Farage can pop up in Mississippi on the Trump campaign – I can’t get Susan Sarandon or Plato out of my mind. Let’s talk first about the actor. When did Plato make a decent movie, eh?

A few weeks ago Sarandon gave a magazine interview to an overawed writer in which she set out her well-known political stall as a radical feminist who backed Bernie Sanders and doesn’t think much of Hillary Clinton. “There’s nothing about her I find feminist except that she’s a woman,” she said.

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Rip-off Britain is going to get worse as the purse strings tighten

From parking fines to airline fares, society’s financialisation is seeing the collective cake shrink as the rich claim an ever larger slice

It is the dog end of August and the sun is shining in many places. A cue for all sorts of predatory people in the thriving British holiday trades to rip off customers who don’t always have a choice and feel ambushed.

In a remote and empty Lake District car park the other day my sister fell foul of an unclear car parking regime. It led to a fine being levied for outstaying the time she had paid for by a few minutes. It happens to us all. In crowded Notting Hill last week, a man told me his car had once been given a penalty notice while he was away at the ticket machine paying his £1.60 for 30 minutes.

Related: Corbyn promises to 'democratise the internet' - Politics live

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The Brexit debate needs more tolerance on both sides | Michael White

Bad sportsmanship is not confined to either camp. Let’s have more signs of mutual respect across the divide

I’m trying to cure this summer’s unattractive impulse before it turns into a bad habit. Whenever I see someone doing something stupid or self-harming like jumping an orange light on a bike or getting tattooed from neck to ankle, I want to shout: “Brexit voter.”

It’s not nice and it’s not fair. I’m trying to stop. As Theresa May’s divided cabinet meets to decide where to go next, ministers and demoralised Whitehall officials should refrain from recrimination too. The “phoney war” lull before the negotiation storm is about to end.

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Can Labour win an election under Corbyn? Readers debate

Catch up on our discussion looking at whether Labour can win under Jeremy Corbyn’s leadership

We’re going to close comments shortly - thanks for taking part in the debate today. We’ll have another one next Thursday lunchtime.

The Labour Party will not win the next general election, but that isn’t the right way of looking at the problem. Labour is in the midst of the same crisis as its sister social-democratic parties across Europe, with one twist: as evidenced by all those new members, it is also home to the kind of new, insurgent politics we’ve seen with Podemos in Spain, Syriza in Greece, the Bernie Sanders campaign in the US etc. Time spent this week at Momentum’s A World Transformed event in Liverpool reminded me that a great deal of Labour and the left’s future lies with some of the people involved (I’ve written a column about this, out later today), but a watershed moment is probably going to be a long time coming.

As things stand, most of what we know takes the form of negatives: that the politics of New Labour are dead, that Labour is dangerously estranged from its old working class base, that the party is pretty much finished in Scotland. What happens next is unclear: my own belief is that it will have involve Labour embracing changing the voting system, creating a politics beyond work and the worker, and understanding that amassing a critical mass of support will involve other forces and parties. All this will take time.

Can Labour win without electoral reform? Certain prominent Labour MPs have been convinced of the merits of proportional representation, and Chris, a reader from Exeter, thinks Labour needs to be thinking in terms of a progressive alliance.

The future of British politics is coalitions and he can lead a combination of Labour / Lib Dem and Greens with support from SNP. He can reach out to those who are outside the current voting patterns and disenfranchised - which is a far greater number is the vote for 16 year olds can be passed.

What really needs to change is our voting system so it takes account of proportional representation. A system where a government is formed out of 40% choice is not representative and also unfair to smaller parties

Thanks everyone, we now have 10 minutes left to discuss. Please get any final points in while you can.

Looking at the Labour party in its current state – confused, conflict-ridden and in desperate need of coherent strategy – it would be easy to assume that electoral success is off the cards for the foreseeable future. Certainly, current polling suggests the party is on track to lose dozens of seats unless something changes.

It’s fairly widely accepted that Labour is in need of some new ideas for the 21st century. Encouragingly, these issues do seem to be being discussed. The Momentum conference fringe event was buzzing with energy and many speakers were tackling difficult topics such as automation and the possibility of a citizens income. Many politicians are also keen to explore similar themes, Jonathan Reynolds MP immediately springs to mind.

How will the triggering of article 50 affect Labour’s chances? If Labour are to benefit from Conservative turmoil over Europe, what line should the party take on negotiations? Jamie, 37, from Sheffield, sees opportunities:

Corbyn undoubtedly needs to reach out to the political centre. But we should not underestimate the trouble brewing for the Tories. This is Theresa May’s honeymoon period but already the cracks are beginning to show. Brexit, specifically the failure to trigger article 50, is a time bomb waiting to go off for the Conservative party. With a slim majority, a Eurosceptic rebellion could see off this government at any moment.

A Labour majority is difficult to imagine. But a coalition with Labour as the largest party? Entirely achievable.

A more optimistic view from a commenter, who believes the terms of the debate - particularly on austerity - have shifted to the extent that Labour’s only viable future is one where it tacks to the left.

Before Corbyn, Labour is going the way of PASOK in Greece - a pro-austerity embarrassment of a Party surviving on the remembered fumes of the Trade Union movement. Since Corbyn became Labour the membership has doubled and the Party has shifted the debate inexorably to the Left. Austerity, as a proclaimed intent, is finished. Not even the Tories can promote themselves as the Party of inequality and free enterprise. Of course, it'll take time for the ideas which have reclaimed the Labour Party to percolate outwards, and it won't be a smooth transition as the Right doing everything in their power to stop Labour, but it's a start of something better.

Readers responding to our form have been making the point that until Labour moves public opinion on key narratives, it’s going to be very difficult for them to make electoral headway. How can the party develop a reputation for economic competence when many voters still blame them for the 2008 economic crash?

Here’s the view of Martin, a registered Labour supporter in Sheffield:

The SNP have shown that the country is ready to elect an anti-austerity government. A government that actually provides excellent public services will find a public willing to bear the cost up to point.

There is a lot that needs to go their way - but I still feel that the main challenge is to change the narrative on the economy. Until we can change the narrative that investment can be positive for the economy, or that cuts aren’t effective in dealing with debt it will be difficult to get anywhere with undecided voters.

This is an interesting comment – making points about the fact that Jeremy Corbyn spent his career on backbenches. What do you think? Is he not very good at preaching to the non-converted? Or is he a man of the people?

No one would think of appointing a CEO of a major company who had no experience at a relatively senior management level, yet this is what the Labour Party has done with Jeremy Corbyn – and Leader of the Opposition is at least as demanding a role as leading a global corporation in terms of the organisational and negotiating skills, strategic vision, stamina, drive, pragmatism and media savviness required.

Corbyn looks like what he is – someone who has spent his entire career on the backbenches, free to follow his own principles and unaccustomed with the burden of having to make compromises and prioritise. And who is now out of his depth.

We’re trying out a new poll tool. Let us know what you think in the comments - and don’t forget to vote!

A commenter below the line makes the reasonable point that it’s all far too early to tell. Given the upheavals seen in domestic and international politics over the past few years, predicting the 2020 election is very difficult - particularly with the full effects of Brexit still to come.

The next election is most likely three and a half years away during which time we will experience the unprecedented upheaval of leaving the EU. There is also issues around boundary changes, scottish independence, the relevance of UKIP, whether labour can resolve their internal issues and divisions within the tory government. So on that basis nobody can say that Labour are not going to win the next election.
In the run up to the 2010 election the tories managed to paint the 2008 crash as caused by Labour and argued they were not economically responsible, yet could not win outright power. And against Gordon Brown of all people.
During the 2015 election campaign the tories maintained the argument, cast Ed Miliband as the son of Britain hater, glorified their own work on the economy since 2010, scapegoated the Lib Dems and saw the SNP all but obliterate Labour in Scotland, yet only managed a 17 seat majority.
Who wins the next election is pure guesswork, mine is that nobody wins outright.

Possible path to victory.
1. An electoral pact. The right win because they always vote together as one big monolith. Our turn. The scare of a small handful of Tories going over to UKIP was enough to panic Cameron into a Brexit referendum. I'm in a supposed Tory safe seat but the truth is that if you counted the Lib Dem and Labour vote together, we would comfortably win. That's repeated up and down the country. An electoral pact means not standing candidates against the most likely to win. It also means people can vote strategically yet maintain allegiance with the party of their conscience.
2. Stand a Labour candidate in Northern Ireland to recover ground lost in Scotland
3. Try and win over the 40% of non-voters.
4. As far as immigration is concerned, it really isn't rocket science. Saying Labour will build 60k new council homes a year is great but it is also arbitrary. Labour should go a bit further and say "we will institute whatever policy is necessary and build however many homes are required to make sure that house and rent prices don't outstrip wages, and if we can't achieve that, we'll look to reduce immigration"

One repeated criticism of Corbyn’s electoral strategy is that he doesn’t do enough to reach out to the centre: the kind of voters with no fixed political allegiance, the kind of voted for Blair in 1997 but were more convinced by David Cameron in 2015.

One ready, a 46 year old Labour member from Brighton, got in touch to say there’s another way of winning: by reaching out to those who don’t currently vote.

At the moment more that 35% of the eligible voters in the UK don’t vote. This is equal to or more than the number of eligible voters that voted Tories to win the last election. Most of these people are mostly not taken into account by pollsters. In my view, Corbyn is connecting with this group of eligible voters. If he can bring them into play in a large number, together with the traditional labour voters that remain loyal to the party, he has a credible path to victory.

An interesting comment from a reader below the line who suggests Corbyn does something to surprise voters.

For Corbyn to win he will need to do something big to convince enough Tories, Liberals and swing voters to vote for him - that's just the mathematical reality. It will be painful for him and his loyal membership perhaps, but he'll need to have at least one or two proposals that make this voting group sit up and say 'wow, I wouldn't have expected him to say that!', it's called cognitive dissonance and is used in advertising to cut through a crowded market place and change brand perceptions.

New Labour understood this; the end of Clause 4, being relaxed about the filthy rich, keeping to Tory spending plans for two years, and making the BoE independent all raised hell in the party, but were highly effective in changing damaging perceptions very quickly and forced the wider electorate to reconsider the brand. There is a downside of course; he will get slated by many on his own side and that hurts, but he has their votes already, he needs to hold his nose and put forward policies that appeal directly to the voters of his opposition.

In a year when Donald Trump’s campaign for the White House has moved from ugly fantasy to likely outcome it would take a very rash old political hack to say without reservation: “Labour cannot win a general election with Jeremy Corbyn as its leader.”

That’s what I think, of course. I do so on the basis of 40 years watching mainstream British politics from a ringside seat inside what my Twitter detractors routinely call the “Westminster bubble” - as if Momentum activists or Ukip Brexiteers don’t live in a tiny confirmation biased bubble of their own.

Comments are now open. For those without a commenting account, there’s also a form you can fill in at the start of the live blog.

We’ve been hearing from Labour members on whether they think the party can turn around its electoral fortunes - keep the views coming, though we’re happy to hear from non-Labour members too. What would it take for you to vote for the party under Corbyn, and what put you off voting for them in 2015?

On opinion, we hear from a Labour member who vows to be more engaged in communicating the party message.

Our engagement isn’t just about reassuring the Labour faithful. The polls are a stark reminder of just how much work there is to do. We must turn the party into a movement that can be radical, and can win. As Corbyn said in his speech at conference, this wave of new members is in fact a “vast democratic resource” – not, as some people see it, a threat.

Related: New Labour members like me need to do more - it’s time to get involved

Labour leader Jeremy Corbyn gave his keynote speech to conference on Wednesday, relaunching his stewardship of the party by outlining his agenda for the country under a Labour government.

Responding to critics who accuse Corbyn of being more interested in campaigning than the more complicated and compromise-strewn business of winning general elections, Corbyn said:

Related: Jeremy Corbyn’s critics must decide: unity or terminal decline | Owen Jones

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Will Britain's exit from the EU be bad for business? Readers debate

Catch up on our debate on Theresa May’s plans to push ahead with Brexit and what this means for workers and business

Nearly four months after June 23’s fateful Brexit vote, even more half baked nonsense is still being talked by both sides than was spouted during the shabby campaign. Nothing is clear except that it is all going to be a lot trickier to disengage from the EU than some foolish people said – and still say despite mounting evidence to the contrary.

So my starting point is one of humility as I learn stuff I didn’t known before. It’s safe to say that some things will be better outside the EU, others worse, some sectors and individuals will thrive, others languish. The consequences of Britain’s leap in the dark – 37% of the total electorate voted Brexit by a very slender margin – are still largely unknown for all 28 members states. Only charlatans and romantics pretend otherwise.

If we left the EU, we would end this sterile debate and we would have to recognize that most of our problems are not caused by Brussels, but by chronic British short termism, inadequate management, sloth, low skills, a culture of easy gratification and underinvestment in both human and physical capital and infrastructure.”

We will be wrapping up the debate in the next four minutes, but we welcome any final comments and remarks.

We will keep comments open until 2.15pm

A view from Nigel Stern, who runs a design agency in London:

The biggest impact will hiring staff with the right skills. It’s already almost impossible to find skilled staff for our design agency - I say this having battled to keep an Australian whose Visa ran out, and lost the battle. I can’t imagine how difficult it will be when Brexit happens. Good skills are literally the biggest growth driver, so for my business Brexit is a disaster waiting to happen

An anonymous take from a bookseller, who thinks that Brexit will be bad for business and will have profound consequences for non-British citizens living and working in the UK.

I am a small on-line antiquarian and used bookseller. Since Brexit I have noticed an uptick in sales to the United States, but I have noticed a distinct decline in sales to Europe, though they do still take place. The effect of Brexit on Europe’s perception of Britain as a country is very negative - and the announcements from the Tory party conference will only reinforce the impression that Britain is not opening up for business. In fact, the very reverse: closing down for business and pursuing policies of discrimination against foreigners, especially from Europe.

The level of discrimination against immigrants from Europe is most definitely alienating what should be Britain’s closest friends. As someone with a slight foreign accent I no longer feel entirely safe in this country. A hard Brexit would be a disaster for me - as many books go abroad and the customs paperwork would add a considerable workload as well as extra costs in the case of more valuable books. There literally is not a single advantage to be derived from Brexit except for the lower pound, which could have been lowered by other means which would have done far less damage to Britain’s economy and society. I don’t know whether in future I will be able to continue business in this country and am wondering whether to move elsewhere.

News of job losses in Scotland are alarming.

The Scottish economy would suffer a severe shock if the UK has a “hard Brexit”, losing up to 80,000 jobs and seeing wages fall by £2,000 a head per year, an economics thinktank has warned.

The Fraser of Allander Institute (FAI) has told the Scottish parliament that entirely leaving the EU single market – known as a hard Brexit – would see the Scottish economy decline by 5% overall, or by £8bn within a decade.

Related: Hard Brexit could cost Scotland £2,000 a head and 80,000 jobs

One commenter says that Brexit will cause some economic pain, although the extent of this is not yet known.

What we know for sure is that Brexit of any substantial kind will certainly cause some economic pain in the short, medium, and long-term, from breaking existing trading relationships and loss of easy access to a large pool of human capital. The additional opportunities, on the other hand, are all long to very long-term, and are uncertain and beyond the UK's control.

Even the bits which are under the UK's control (like massive investment in training and education in a way which actually achieves something instead of pfaffing around with needless re-structuring and testing kids to the edge of mental breakdown) are all things that would have made sense before, so it's optimistic to imagine that they'll happen in a future where the public finances are under more pressure than ever before (once Brexit decline takes hold).

Here’s a view from Richard Rose, who is worried about Brexit’s impact on the car industry.

I am an engineer working at Rolls-Royce in Derby but I have spent most of my working life so far in the car industry. I am 100% certain that if the UK Brexits out of the single market, it can wave ¾ of its car industry goodbye within 5 years. The idea of replacing the current arrangement with one of tit-for-tat tariffs on cars sold into and out of the UK is preposterous – we will be in the absurd situation of paying taxpayers’ cash to car companies in the form of ongoing subsidies, and every successive government will be looking for ways to reduce or avoid these payments every four years.

The whole arrangement sounds ridiculous and seeing as all the manufacturers who build here have sites inside the Eurozone where they can avoid all that uncertainty, what do you think they’ll do? Its keeping me awake at night as I feel ‘my’ industry is potentially about to be rendered economically unviable just as my right to live and work abroad is being curtailed.

Quitting the European Union’s single market is considered bad for business unless you belong to the small band of economists who believe that Brussels’ employment and environmental protections stifle innovation, that maintaining a low pound is easier outside the EU, and restrictions on migrants is unlikely to ever be enforced.

But the threat from Nissan to switch investment in its next car away from the north east without some form of compensation is the clearest indication yet that multinationals based in the UK to benefit from the single market are going to drift away as they consider an upgrade or new factory that would be cheaper abroad.

John Flahive, 51, a documentary producer and sales agent, is concerned about the implications of a “hard Brexit” on his business.

The impact on business is inevitably negative. At the moment we have free movement of goods throughout the EU, all I have to do in my own business is put an address on a shipment and off it goes. It’s just not possible for whatever is put in its place to improve on that.

A ‘trade deal’ usually involves reduced tariffs which is a dis-improvement on no tariffs at all. This would bring back customs paperwork and all the associated admin, whereas currently we have none at all. There is no upside, only a downside.

This has just launched online. Polly Toynbee asks why the health secretary would insult the one third of our doctors who were born abroad by suggesting that they’re only “interim”.

Hunt’s claim that we will be “self-sufficient” in medical staff is nonsense – and he knows it. These new doctors won’t qualify as consultants until 2030, while everywhere has ageing populations and the WHO estimates a global shortage of 2 million doctors. The number of people in Britain over the age of 85 will double by 2037 – and who is to care for them if we chase away all foreigners?

Related: Telling NHS doctors to go home is self-harming madness | Polly Toynbee

An interesting take from one commenter below the line:

The main reason I don't think it'll be good for business is the way it is and has effected Britain's image around Europe and probably the world. Made in Britain isn't actually very popular in Europe at the moment. When I am with my girlfriend in Spain what image of Britain is on the television? Farage, Boris Johnson and their xenophobic rhetoric. After all it's the consumers who are the most important when it comes to our exports. Do you really want to buy goods from a nation who's image is one of distaste and xenophobia to their neighbours. Look at the effect the Iraq war had on French products in the U.S when they went ( rightfully ) against the Iraq war.... Everything Farage and Boris do is making it far easier for the E.U to take a tough stance in negotiations with support from their people. Especially when they act so arrogantly by saying the E.U has too much to lose and will have to take any deal we offer.

Brexiters seem to have no idea on how politics will effect us more than anything else.

Comments are open below the line and our debate is underway.

Kicking us off from the form is a small business owner in the south east of England, who has noted a definite impact of the vote:

I’ve already seen an impact in car buying attitudes in the months following the referendum. Traditionally, September is a busy time for my business (my company move new and used cars around the U.K.) and already the volume of movements compared to March and this time last year is worrying.

Every dealership I visit, staff say the same thing; “It’s unusually quite for this time of year”. The uncertainty created by the referendum is clearly having an affect and I worry for the future of my business once article 50 is triggered. If people are out of work they won’t be buying cars, meaning I won’t be moving them round the U.K.

Polly Toynbee raised some interesting questions about the impact of hard Brexit this week. She wrote:

As speech after speech salutes “taking back control” as “a fully independent sovereign country”, only old sober-sides Philip Hammond throws cold water. There is a price to pay, he warns. He didn’t disagree with Institute for Fiscal Studies estimates that Brexit will cost the UK 4% in growth in coming years.

Related: Will Theresa May be the next Tory leader to be bulldozed by the Europhobes? | Polly Toynbee

Theresa May made one thing perfectly clear during this year’s Conservative party conference: Brexit means Brexit.

The Tory leader said controlling immigration and withdrawing from the jurisdiction of the European court of justice would be her priorities during European Union (EU) exit. She says Article 50 will be triggered before the end of March 2017.

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Michael White reflects on 45 years as a Guardian journalist

As the former political editor and columnist retires, he considers his career at the paper and the greatest scoop he never wrote

Michael White, the Guardian’s assistant editor, retired last week after almost 45 years at the paper as a reporter, foreign correspondent and columnist. He was political editor from 1990-2006, Washington correspondent (1984-88) and parliamentary sketch writer (1977-84). Here he reflects on his Guardian career.

When did you first know you wanted to be a journalist?
I was never a student journalist but, after failing a few interviews for industry in my final student year, I decided – correctly – that I am by nature an observer, not a doer. I was lucky in my timing: 1966 was a very good time to embark on a career in journalism.

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How to change a prime minister – Politics Weekly podcast

Jessica Elgot is joined by Michael White, Katy Balls and John Crace to discuss Theresa May’s future. Also this week: Jonathan Holslag explains how patterns in history can help us predict today’s political upheavals

After a week in which anonymous Tory MPs briefed violent rhetoric to the Sunday papers, and rumours once again swirled around Westminster about a confidence vote, Theresa May faced down her critics at the Conservative party’s 1922 Committee.

She emerged looking stronger than she has for weeks, but for how long can she continue to survive in her own hostile environment?

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From the archive: Coca-Cola changes its formula – 25 April 1985

25 April 1985: The new taste is said to be smoother, rounder and bolder, not to mention more harmonious

The hard-nosed men of the New York Stock Exchange yesterday made a snap judgment on the most sensational news in the mighty American soft drinks industry for 99 years. Without even trying the new, sweeter formula Coca-Cola, they backed the initial shock reaction of the amateurs: it tastes more like Pepsi.

By lunchtime yesterday Coca-Cola shares had taken another 1.50 cent pounding on top of the 1.60 they sustained in late trading after the new formula was officially unveiled on Monday, despite the assurances of Coke’s chairman, Mr Roberto Goizueta, that the new taste is smoother, rounder and bolder, not to mention more harmonious. Reporters disagreed.

Related: Milk Coke: another classic from the nation that invented Cheeky Vimto

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How Theresa May’s exit compares with other difficult departures from No 10

The Guardian’s former political editor revisits humiliating prime ministerial resignations from Robert Peel to David Cameron

Both Brexit camps claim Sir Robert Peel, the Tory moderniser whose 1846 resignation crisis most resembles May’s. But he had succeeded where she failed. Determined to cut food prices for industrial workers, Peel pushed through repeal of protectionist Corn Laws with opposition help. In retaliation, rightwing enemies defeated his Irish Coercion bill. Peel resisted Queen Victoria’s appeal to stay, but grateful crowds cheered him as he walked to the Commons to resign. He slipped out by a side door, but was spotted and cheered home. Divided Tories lost office for 20 years.

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