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Donald Trump dined with white nationalist, Holocaust denier Nick …
This past week, Kanye West called me to have dinner at Mar-a-Lago, he wrote. Shortly thereafter, he unexpectedly showed up with three of his friends, whom I knew nothing about. We had dinner on Tuesday evening with many members present on the back patio. The dinner was quick and uneventful. They then left for the airport.
However eventful, the dinner reflects a remarkable moment in an extremely early 2024 campaign cycle: the frontrunner for the Republican presidential nomination breaking bread with a man who frequently posts racist content and Holocaust revisionism, brought there by a rapper who is launching his own presidential campaign under the shadow of his own antisemitic remarks.
If it was any other party, breaking bread with Nick Fuentes would be instantly disqualifying for Trump, said Democratic National Committee spokesperson Ammar Moussa. The most extreme views have found a home in todays MAGA Republican party.
In a statement, the White House said, Bigotry, hate, and antisemitism have absolutely no place in America - including at Mar-A-Lago. Holocaust denial is repugnant and dangerous, and it must be forcefully condemned.
It underscores how few guardrails currently exist within the former presidents political operation, with few aides there to screen guests or advise against and manage such gatherings.
Indeed, after POLITICO first reported the sighting of Fuentes at Trumps club, people in Trumps orbit denied the former president met with Fuentes at all. Only later was it revealed that he not only met with Fuentes but dined with him.
Karen Giorno, a former Trump strategist who is also now working for Wests 2024 campaign, confirmed to POLITICO that she was also at the dinner with Trump, West and Fuentes.
Fuentes, who was present at the Charlottesville Unite the Right rally in 2017, has made a series of offensive and racist statements on his shows including that Trump was wrong to disavow white supremacy. He has been removed from YouTube and other social media sites. Trumps dinner with Fuentes comes just one week after the former president announced he is seeking reelection, and soon after West publicly made a series of antisemitic comments that cost him millions in endorsement deals.
In a separate statement, Trump denied knowing who Fuentes was, stating that the dinner meeting was intended to be Kanye and me only, but he arrived with a guest whom I had never met and knew nothing about. Both that statement and the Truth Social post did not include a denunciation of Wests or Fuentes recent comments.
West discussed the dinner in a video titled Mar-a-lago debrief, which he posted to Twitter. In it, he said that Trump was impressed by Fuentes because unlike so many of the lawyers and so many people that he was left with on his 2020 campaign, hes actually a loyalist.
West went on to say he told Trump, Why when you had the chance, did you not free the January sixers? And I came to him as someone who loves Trump. And I said, Go and get Corey [Lewandowski] back, go and get these people that the media tried to cancel and told you to step away from. The video includes photos of former advisers including Giorno and Roger Stone, and also conspiracy theorist Alex Jones.
Describing the event to Milo Yiannopoulos, a far-right provocateur who he hired to help with his campaign, West said that he also asked Trump to be his running mate in 2024, and said that Trump was screaming at him during the dinner, and that the former president called his ex-wife profanities.
When Trump started basically screaming at me at the table, telling me I was going to lose. I mean, has that ever worked for anyone in history? Im like, whoa, whoa, hold on, hold on Trump, youre talking to Ye, West said.
Chris Cadelago contributed to this report.
CORRECTION: An earlier version of this report misspelled the first name of Corey Lewandowski.
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Donald Trump dined with white nationalist, Holocaust denier Nick ...
Trump talks with white nationalist Nick Fuentes at Mar-a-Lago dinner
Nick Fuentes (center) with Alex Jones at a "Stop the Steal" rally in Georgia on Nov. 19, 2020. Photo: Zach Roberts/NurPhoto via Getty Images
Former President Trump dined and conversed with white nationalist Nick Fuentes and rapper Ye, formerly known as Kanye West, at his Mar-a-Lago resort on Tuesday night, according to two sources familiar with the matter.
Why it matters: Trump's direct engagement with a man labeled a "white supremacist" by the Justice Department, one week after declaring his 2024 candidacy, is likely to draw renewed outrage over the former president's embrace of extremists.
What they're saying: "Kanye West very much wanted to visit Mar-a-Lago. Our dinner meeting was intended to be Kanye and me only, but he arrived with a guest whom I had never met and knew nothing about," Trump said in a statement.
Bigotry, hate, and antisemitism have absolutely no place in America - including at Mar-A-Lago," White House Deputy Press Secretary Andrew Bates said Saturday in a statement.
Behind the scenes: A source familiar with the dinner conversation told Axios that Trump "seemed very taken" with Fuentes, impressed that the 24-year-old was able to rattle off statistics and recall speeches dating back to his 2016 campaign.
Fuentes told Trump that he represented a side of Trump's base that was disappointed with his newly cautious approach, especially with what some far-right activists view as a lack of support for those charged in the Jan. 6 Capitol attack.
Trump at one point turned to Ye and said, "I really like this guy. He gets me," according to the source.
Trump asked if Fuentes was on social media such as Truth Social, the former president's alternative to Twitter.
Driving the news: Ye, whose Twitter account was recently restored after being restricted for anti-Semitic comments, posted a video on Thursday night titled "Mar-a-Lago debrief."
Between the lines: The Daily Beast reported Wednesday that Fuentes was not present at the Mar-a-Lago dinner with Ye, citing a source familiar with the matter.
Flashback: Truth Social, Trump's social media platform, sparked backlash by verifying Fuentes' account in February.
Editor's note: This story has been updated with additional reporting and a statement from Trump and the White House.
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Trump talks with white nationalist Nick Fuentes at Mar-a-Lago dinner
Donald Trump dined with white nationalist, Holocaust denier Nick Fuentes
Former President Donald Trump hosted white nationalist and antisemite Nick Fuentes at his Mar-a-Lago resort in Palm Beach on Tuesday night, according to multiple people familiar with the event.
Fuentes, who frequently posts racist content in addition to Holocaust revisionism, was brought as a guest of rapper Kanye West, who now goes by Ye.
In a post to his social media site, Trump confirmed the gathering.
This past week, Kanye West called me to have dinner at Mar-a-Lago, he wrote. Shortly thereafter, he unexpectedly showed up with three of his friends, whom I knew nothing about. We had dinner on Tuesday evening with many members present on the back patio. The dinner was quick and uneventful. They then left for the airport.
However eventful, the dinner reflects a remarkable moment in an extremely early 2024 campaign cycle: the frontrunner for the Republican presidential nomination breaking bread with a man who frequently posts racist content and Holocaust revisionism, brought there by a rapper who is launching his own presidential campaign under the shadow of his own antisemitic remarks.
If it was any other party, breaking bread with Nick Fuentes would be instantly disqualifying for Trump," said Democratic National Committee spokesperson Ammar Moussa. "The most extreme views have found a home in todays MAGA Republican party.
In a statement, the White House said, "Bigotry, hate, and antisemitism have absolutely no place in America - including at Mar-A-Lago. Holocaust denial is repugnant and dangerous, and it must be forcefully condemned.
It underscores how few guardrails currently exist within the former presidents political operation, with few aides there to screen guests or advise against and manage such gatherings.
Indeed, after POLITICO first reported the sighting of Fuentes at Trumps club, people in Trumps orbit denied the former president met with Fuentes at all. Only later was it revealed that he not only met with Fuentes but dined with him.
Story continues
Karen Giorno, a former Trump strategist who is also now working for Wests 2024 campaign, confirmed to POLITICO that she was also at the dinner with Trump, West and Fuentes.
Fuentes, who was present at the Charlottesville Unite the Right rally in 2017, has made a series of offensive and racist statements on his shows including that Trump was wrong to disavow white supremacy. He has been removed from YouTube and other social media sites. Trumps dinner with Fuentes comes just one week after the former president announced he is seeking reelection, and soon after West publicly made a series of antisemitic comments that cost him millions in endorsement deals.
In a separate statement, Trump denied knowing who Fuentes was, stating that the dinner meeting was intended to be Kanye and me only, but he arrived with a guest whom I had never met and knew nothing about. Both that statement and the Truth Social post did not include a denunciation of West's or Fuentes' recent comments.
West discussed the dinner in a video titled Mar-a-lago debrief, which he posted to Twitter. In it, he said that Trump was impressed by Fuentes because unlike so many of the lawyers and so many people that he was left with on his 2020 campaign, he's actually a loyalist."
West went on to say he told Trump, Why when you had the chance, did you not free the January sixers? And I came to him as someone who loves Trump. And I said, Go and get Corey [Lewandowski] back, go and get these people that the media tried to cancel and told you to step away from. The video includes photos of former advisers including Giorno and Roger Stone, and also conspiracy theorist Alex Jones.
Describing the event to Milo Yiannopoulos, a far-right provocateur who he hired to help with his campaign, West said that he also asked Trump to be his running mate in 2024, and said that Trump was screaming at him during the dinner, and that the former president called his ex-wife profanities.
"When Trump started basically screaming at me at the table, telling me I was going to lose. I mean, has that ever worked for anyone in history? Im like, whoa, whoa, hold on, hold on Trump, youre talking to Ye, West said.
Chris Cadelago contributed to this report.
CORRECTION: An earlier version of this report misspelled the first name of Corey Lewandowski.
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Donald Trump dined with white nationalist, Holocaust denier Nick Fuentes
Deep Mind AlphaTensor Will Discover New Algorithms
Deep Mind has extended AlphaZero to mathematics to unlock new possibilities for research Algorithms.
AlphaTensor, builds upon AlphaZero, an agent that has shown superhuman performance on board games, like chess, Go and shogi, and this work shows the journey of AlphaZero from playing games to tackling unsolved mathematical problems for the first time.
The ancient Egyptians created an algorithm to multiply two numbers without requiring a multiplication table, and Greek mathematician Euclid described an algorithm to compute the greatest common divisor, which is still in use today.
During the Islamic Golden Age, Persian mathematician Muhammad ibn Musa al-Khwarizmi designed new algorithms to solve linear and quadratic equations. In fact, al-Khwarizmis name, translated into Latin as Algoritmi, led to the term algorithm. But, despite the familiarity with algorithms today used throughout society from classroom algebra to cutting edge scientific research the process of discovering new algorithms is incredibly difficult, and an example of the amazing reasoning abilities of the human mind.
They published in Nature. AlphaTensor is the first artificial intelligence (AI) system for discovering novel, efficient, and provably correct algorithms for fundamental tasks such as matrix multiplication. This sheds light on a 50-year-old open question in mathematics about finding the fastest way to multiply two matrices.
Trained from scratch, AlphaTensor discovers matrix multiplication algorithms that are more efficient than existing human and computer-designed algorithms. Despite improving over known algorithms, they note that a limitation of AlphaTensor is the need to pre-define a set of potential factor entries F, which discretizes the search space but can possibly lead to missing out on efficient algorithms. An interesting direction for future research is to adapt AlphaTensor to search for F. One important strength of AlphaTensor is its flexibility to support complex stochastic and non-differentiable rewards (from the tensor rank to practical efficiency on specific hardware), in addition to finding algorithms for custom operations in a wide variety of spaces (such as finite fields). They believe this will spur applications of AlphaTensor towards designing algorithms that optimize metrics that we did not consider here, such as numerical stability or energy usage.
The discovery of matrix multiplication algorithms has far-reaching implications, as matrix multiplication sits at the core of many computational tasks, such as matrix inversion, computing the determinant and solving linear systems.
The process and progress of automating algorithmic discoveryFirst, they converted the problem of finding efficient algorithms for matrix multiplication into a single-player game. In this game, the board is a three-dimensional tensor (array of numbers), capturing how far from correct the current algorithm is. Through a set of allowed moves, corresponding to algorithm instructions, the player attempts to modify the tensor and zero out its entries. When the player manages to do so, this results in a provably correct matrix multiplication algorithm for any pair of matrices, and its efficiency is captured by the number of steps taken to zero out the tensor.
This game is incredibly challenging the number of possible algorithms to consider is much greater than the number of atoms in the universe, even for small cases of matrix multiplication. Compared to the game of Go, which remained a challenge for AI for decades, the number of possible moves at each step of their game is 30 orders of magnitude larger (above 10^33 for one of the settings they consider).
Essentially, to play this game well, one needs to identify the tiniest of needles in a gigantic haystack of possibilities. To tackle the challenges of this domain, which significantly departs from traditional games, we developed multiple crucial components including a novel neural network architecture that incorporates problem-specific inductive biases, a procedure to generate useful synthetic data, and a recipe to leverage symmetries of the problem.
They then trained an AlphaTensor agent using reinforcement learning to play the game, starting without any knowledge about existing matrix multiplication algorithms. Through learning, AlphaTensor gradually improves over time, re-discovering historical fast matrix multiplication algorithms such as Strassens, eventually surpassing the realm of human intuition and discovering algorithms faster than previously known.
Exploring the impact on future research and applicationsFrom a mathematical standpoint, their results can guide further research in complexity theory, which aims to determine the fastest algorithms for solving computational problems. By exploring the space of possible algorithms in a more effective way than previous approaches, AlphaTensor helps advance our understanding of the richness of matrix multiplication algorithms. Understanding this space may unlock new results for helping determine the asymptotic complexity of matrix multiplication, one of the most fundamental open problems in computer science.
Because matrix multiplication is a core component in many computational tasks, spanning computer graphics, digital communications, neural network training, and scientific computing, AlphaTensor-discovered algorithms could make computations in these fields significantly more efficient. AlphaTensors flexibility to consider any kind of objective could also spur new applications for designing algorithms that optimise metrics such as energy usage and numerical stability, helping prevent small rounding errors from snowballing as an algorithm works.
While they focused here on the particular problem of matrix multiplication, we hope that our paper will inspire others in using AI to guide algorithmic discovery for other fundamental computational tasks. Their research also shows that AlphaZero is a powerful algorithm that can be extended well beyond the domain of traditional games to help solve open problems in mathematics. Building upon our research, they hope to spur on a greater body of work applying AI to help society solve some of the most important challenges in mathematics and across the sciences.
Nature Discovering faster matrix multiplication algorithms with reinforcement learning
AbstractImproving the efficiency of algorithms for fundamental computations can have a widespread impact, as it can affect the overall speed of a large amount of computations. Matrix multiplication is one such primitive task, occurring in many systemsfrom neural networks to scientific computing routines. The automatic discovery of algorithms using machine learning offers the prospect of reaching beyond human intuition and outperforming the current best human-designed algorithms. However, automating the algorithm discovery procedure is intricate, as the space of possible algorithms is enormous. Here we report a deep reinforcement learning approach based on AlphaZero1for discovering efficient and provably correct algorithms for the multiplication of arbitrary matrices. Our agent, AlphaTensor, is trained to play a single-player game where the objective is finding tensor decompositions within a finite factor space. AlphaTensor discovered algorithms that outperform the state-of-the-art complexity for many matrix sizes. Particularly relevant is the case of 44 matrices in a finite field, where AlphaTensors algorithm improves on Strassens two-level algorithm for the first time, to our knowledge, since its discovery 50 years ago2. We further showcase the flexibility of AlphaTensor through different use-cases: algorithms with state-of-the-art complexity for structured matrix multiplication and improved practical efficiency by optimizing matrix multiplication for runtime on specific hardware. Our results highlight AlphaTensors ability to accelerate the process of algorithmic discovery on a range of problems, and to optimize for different criteria.
Brian Wang is a Futurist Thought Leader and a popular Science blogger with 1 million readers per month. His blog Nextbigfuture.com is ranked #1 Science News Blog. It covers many disruptive technology and trends including Space, Robotics, Artificial Intelligence, Medicine, Anti-aging Biotechnology, and Nanotechnology.
Known for identifying cutting edge technologies, he is currently a Co-Founder of a startup and fundraiser for high potential early-stage companies. He is the Head of Research for Allocations for deep technology investments and an Angel Investor at Space Angels.
A frequent speaker at corporations, he has been a TEDx speaker, a Singularity University speaker and guest at numerous interviews for radio and podcasts. He is open to public speaking and advising engagements.
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Take a Deep Breath – The American Institute of Stress
For many of us, relaxation means zoning out in front of the TV at the end of a stressful day. But this does little to reduce the damaging effects of stress. To effectively combat stress, we need to activate the bodys natural relaxation response. The Relaxation Response was discovered and coined by AIS Founding Trustee and Fellow,Dr. Herbert Benson . The relaxation response is a physical state of deep rest that changes the physical and emotional responses to stress (e.g., decreases in heart rate, blood pressure, rate of breathing, and muscle tension).
When eliciting the relaxation response:
Your metabolism decreases
Your heart beats slower and your muscles relax
Your breathing becomes slower
Your blood pressure decreases
Your levels of nitric oxide are increased
At AIS we are often asked, What is the best way to relive my stress and relax? Our typical answer includes an explanation that just as the definition of stress is different for everyone, so are the best stress reduction techniques. However, there is one Super Stress Buster that evokes the relaxation response that we widely recommend as useful for everyone- even kids. Can you guess what it is? BREATHING! That is right, simply breathing. It is free and can be practiced anywhere- I bet you are even breathing right now! The key, of course, is focused breathing.
The relaxation response is not lying on the couch or sleeping but a mentally active process that leaves the body relaxed, calm, and focused.
Abdominal breathing for 20 to 30 minutes each day will reduce anxiety and reduce stress. Deep breathing increases the supply of oxygen to your brain and stimulates the parasympathetic nervous system, which promotes a state of calmness. Breathing techniques help you feel connected to your bodyit brings your awareness away from the worries in your head and quiets your mind.
AIS endorses several breathing techniques and even a few tools that can be useful for progression in mastering your breathing, reconnecting your body and mind and stopping the stress response.
1. Quieting Response utilizes visualization and deep breathing (a powerful combination) to stop an acute stress response in its tracks. The entire exercise only takes 6 seconds! First smile inwardly with your eyes and mouth and release the tension in your shoulders. This is a powerful muscle release in the places where most people hold their muscles tense. Then imagine holes in the soles of your feet. As you take a deep breath in, visualize hot air flowing through these holes moving slowly up your legs, through your abdomen and filling your lungs. Relax your muscles sequentially as the hot air moves through them up your body. When you exhale reverse the visualization so you see hot air coming out the same holes in your feet. Repeat throughout the day whenever you need to feel calm and relaxed.
2. Sudarshan Kriya or SKY incorporates specific natural rhythms of the breath which harmonize the body, mind and emotions. This unique breathing technique eliminates stress, fatigue and negative emotions such as anger, frustration and depression, leaving you calm yet energized, focused yet relaxed. There are a series of exercises that you can practice to find relief. To read more about SKY visit one of our new AIS Certified organizations: The Art of Living at http://www.artofliving.org. We will soon post several Art of Living breath courses in our Learning Center.
3. This one is for kidsTeddy Bear Breathing Lie on your back, place one hand on your chest and place your favorite teddy bear on your belly button. Close your eyes and relax your whole body. Breath in slowly through your nose. Your teddy bear should slowly rise, but your chest should not. When you have taken a full deep breath, hold it, count to three then slowly breathe out. Repeat a few times, until your feel relaxed.
1. Stress Eraser-The StressEraser is an award-winning portable biofeedback device that helps you learn to activate your bodys natural relaxation response in minutes without the use of medication. Read More
2. EmWave-The emWave 2 and the emWave Desktop is a scientifically validated heart-rate monitoring system that facilitates learning techniques to create an optimal state in which the heart, mind and emotions are operating in-sync and balanced. Read More
Learning the basics of these breathing techniques isnt difficult, but it does take practice. AIS stress experts recommend setting aside at least 10 to 20 minutes a day for your relaxation practice. If that sounds like a daunting commitment, remember that many of these techniques can be incorporated into your existing daily schedulepracticed at your desk over lunch or on the bus during your morning commute.
If possible, schedule a set time to practice each day. Set aside one or two periods each day. You may find that its easier to stick with your practice if you do it first thing in the morning, before other tasks and responsibilities get in the way.
Practice relaxation techniques while youre doing other things. Meditate while commuting to work on a bus or train, or waiting for a dentist appointment. Try deep breathing while youre doing housework or mowing the lawn. Mindfulness walking can be done while exercising your dog, walking to your car, or climbing the stairs at work instead of using the elevator. Once youve learned techniques such as tai chi or yoga, you can practice them in your office or in the park at lunchtime.
If you exercise, improve the relaxation benefits by adopting mindfulness. Instead of zoning out or staring at a TV as you exercise, try focusing your attention on your body. If youre resistance training, for example, focus on coordinating your breathing with your movements and pay attention to how your body feels as you raise and lower the weights.
Avoid practicing when youre sleepy. These techniques can relax you so much that they can make you very sleepy, especially if its close to bedtime. You will get the most benefit if you practice when youre fully awake and alert. Do not practice after eating a heavy meal or while using drugs, tobacco, or alcohol. Absolutely do not practice any relaxation technique that might make you drowsy while driving.
Expect ups and downs. Dont be discouraged if you skip a few days or even a few weeks. It happens. Just get started again and slowly build up to your old momentum.
I want to hear from you. Do you use focused breathing to reduce stress? What works, what doesnt? Post a comment here or start a conversation in the AIS forum. To read more about these and other stress topics visit The American Institute of Stresss website: http://www.stress.org
Contributed by: Kellie Marksberry
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xkcd: Free Speech
xkcd: Free SpeechPreorder What If? 2 (all US preorders eligible) and enter our contest for a chance to win a dedicated comic and What If blog post!
Free Speech
[[A person speaking to the reader.]]Person: Public Service Announcehment: The *right to free speech* means the government can't arrest you for what you say.[[Close-up on person's face.]]Person: It doesn't mean that anyone else has to listen to your bullshit, - or host you while you share it.[[Back to full figure.]]Person: The 1st Amendment doesn't shield you from criticism or consequences.[[Close-up.]]Person: If you're yelled at, boycotted, have your show canceled, or get banned from an internet community, your free speech rights aren't being violated.[[Person, holding palm upward.]]Person: It's just that the people listening think you're an asshole,[[A door that is ajar.]]Person: And they're showing you the door.{{Title text: I can't remember where I heard this, but someone once said that defending a position by citing free speech is sort of the ultimate concession; you're saying that the most compelling thing you can say for your position is that it's not literally illegal to express.}}
This work is licensed under aCreative Commons Attribution-NonCommercial 2.5 License.
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Free Speech | American Civil Liberties Union
Freedom of expression is the matrix, the indispensable condition, of nearly every other form of freedom.
U.S. Supreme Court Justice Benjamin N. Cardozo in Palko v. Connecticut
Freedom of speech, the press, association, assembly, and petition: This set of guarantees, protected by the First Amendment, comprises what we refer to as freedom of expression. It is the foundation of a vibrant democracy, and without it, other fundamental rights, like the right to vote, would wither away.
The fight for freedom of speech has been a bedrock of the ACLUs mission since the organization was founded in 1920, driven by the need to protect the constitutional rights of conscientious objectors and anti-war protesters. The organizations work quickly spread to combating censorship, securing the right to assembly, and promoting free speech in schools.
Almost a century later, these battles have taken on new forms, but they persist. The ACLUs Speech, Privacy, and Technology Project continues to champion freedom of expression in its myriad forms whether through protest, media, online speech, or the arts in the face of new threats. For example, new avenues for censorship have arisen alongside the wealth of opportunities for speech afforded by the Internet. The threat of mass government surveillance chills the free expression of ordinary citizens, legislators routinely attempt to place new restrictions on online activity, and journalism is criminalized in the name of national security. The ACLU is always on guard to ensure that the First Amendments protections remain robust in times of war or peace, for bloggers or the institutional press, online or off.
Over the years, the ACLU has represented or defended individuals engaged in some truly offensive speech. We have defended the speech rights of communists, Nazis, Ku Klux Klan members, accused terrorists, pornographers, anti-LGBT activists, and flag burners. Thats because the defense of freedom of speech is most necessary when the message is one most people find repulsive. Constitutional rights must apply to even the most unpopular groups if theyre going to be preserved for everyone.
Some examples of our free speech work from recent years include:
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Is Alex Jones’ trial about free speech rights? | AP News
CHICAGO (AP) Conspiracy theorist Alex Jones arrived at a Texas courthouse for his defamation trial for calling the Sandy Hook Elementary School attack a hoax with the words Save the 1st scrawled on tape covering his mouth.
Although Jones portrays the lawsuit against him as an assault on the First Amendment, the parents who sued him say his statements were so malicious and obviously false that they fell well outside the bounds of speech protected by the constitutional clause.
The ongoing trial in Austin, which is where Jones far-right Infowars website and its parent company are based, stems from a 2018 lawsuit brought by Neil Heslin and Scarlett Lewis, whose 6-year-old son was killed in the 2012 attack along with 19 other first-graders and six educators.
Jones took the stand Tuesday and Wednesday in his own defense.
Heres a look at how the case relates to the First Amendment:
ARE ALL DEFAMATION LAWSUITS FIRST AMENDMENT CASES?
They are. Defamation laws evolved through decades of U.S. Supreme Court rulings on what is and isnt protected speech.
Typically, the first question jurors answer at trials is whether the speech qualifies as unprotected defamation. If it does, they address the question of damages.
Jones trial largely skipped the first question and went straight to the second. From the start, it focused not on whether Jones must pay damages, but how much.
WHY IS HIS TRIAL DIFFERENT?
Jones seemed to sabotage his own chance to fully argue that his speech was protected by not complying with orders to hand over critical evidence, such as emails, which the parents hoped would prove he knew all along that his statements were false.
That led exasperated Judge Maya Guerra Gamble to enter a rare default judgment, declaring the parents winners before the trial even began.
Judges in other lawsuits against Jones have issued similar rulings.
I dont know why they didnt cooperate, said Stephen D. Solomon, a founding editor of New York Universitys First Amendment Watch. It is just really peculiar. ... Its so odd to not even give yourself the chance to defend yourself.
It might suggest Jones knew certain evidence would doom his defense.
It is reasonable to presume that (Jones) and his team did not think they had a viable defense ... or they would have complied, said Barry Covert, a Buffalo, New York, First Amendment lawyer.
HAVE BOTH SIDES REFERRED TO THE FIRST AMENDMENT?
Yes. During opening statements last week, plaintiffs lawyer Mark Bankston told jurors it doesnt protect defamatory speech.
Speech is free, he said, but lies you have to pay for.
Jones lawyer Andino Reynal said the case is crucial to free speech.
And Jones made similar arguments in a deposition.
If questioning public events and free speech is banned because it might hurt somebodys feelings, we are not in America anymore, he said.
Jones, who had said actors staged the shooting as a pretext to strengthen gun control, later acknowledged it occurred.
WHAT ARE KEY ELEMENTS OF DEFAMATION?
Defamation must involve someone making a false statement of fact publicly typically via the media and purporting that its true. An opinion cant be defamatory. The statement also must have done actual damage to someones reputation.
The parents suing Jones say his lies about their childs death harmed their reputations and led to death threats from Jones followers.
IS IT EASIER FOR NON-PUBLIC FIGURES TO PROVE DEFAMATION?
Yes. They must merely show a false statement was made carelessly.
In New York Times v. Sullivan in 1964, the Supreme Court said the bar for public figures must be higher because scrutiny of them is so vital to democracy. They must prove actual malice, that a false statement was made with knowledge that it was false or with reckless disregard of whether it was false or not.
ARE THE PARENTS PUBLIC FIGURES?
Their lawyers say they clearly arent in the category of politicians or celebrities who stepped voluntarily into the public arena.
The high court, however, has said those who temporarily enter public debates can become temporary public figures.
Jones argues that Heslin did just that, entering the national debate over guns by advocating for tougher gun laws on TV and before Congress.
WHAT DAMAGES ARE BEING SOUGHT?
The plaintiffs are seeking $150 million for emotional distress, as well as reputational and punitive damages.
Reynal told jurors that his client has been punished enough, losing millions of dollars being booted off major social media platforms.
He asked them to award the plaintiffs $1.
CAN FIRST AMENDMENT ISSUES INFLUENCE THE TRIALS OUTCOME?
Indirectly, yes.
Jones cant argue that hes not liable for damages on the grounds that his speech was protected. The judge already ruled he is liable. But as a way to limit damages, his lawyers can argue that his speech was protected.
Jurors could say (Jones defamatory statements) is actually something we dont want to punish very hard, said Kevin Goldberg, a First Amendment specialist at the Maryland-based Freedom Forum.
COULD JONES HAVE WON IF THE TRIAL WAS ALL ABOUT FREE SPEECH?
He could have contended that his statements were hyperbolic opinion that wild, non-factual exaggeration is his schtick.
But it would have been tough to persuade jurors that he was merely riffing and opining.
It was a verifiable fact the massacre occurred at Sandy Hook, said Solomon. Thats not opinion. It is a fact. Even if the parents were deemed public figures, imposing the higher standard, I think Alex Jones would still lose, he said.
But Covert said defamation is always a challenge to prove.
I wouldnt discount the possibility Jones could have prevailed, he said. Trying to speculate what a jury would find is always a fools errand.
MIGHT THE SUPREME COURT BE SYMPATHETIC TO ANY JONES APPEAL?
Conservatives and liberal justices have found that some deeply offensive speech is protected.
In 2011, the high court voted 8-to-1 to overturn a verdict against the Kansas-based Westboro Baptist Church for picketing military funerals with signs declaring that God hates the U.S. for tolerating homosexuality.
As a Nation we have chosen ... to protect even hurtful speech ... to ensure that we do not stifle public debate, the ruling said.
But it and the Jones case have key differences.
They were both extreme, outrageous, shocking, deplorable. But the Westboro Baptist Church was also manifestly political and not defamatory ... not about any one persons reputation Goldberg said.
He added: Id be shocked if (Jones) case ever ended up in the Supreme Court.
___
For more of the APs coverage of school shootings: https://apnews.com/hub/school-shootings
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Opinion | America Has a Free Speech Problem – The New York Times
At the same time, all Americans should be deeply concerned about an avalanche of legislation passed by Republican-controlled legislatures around the country that gags discussion of certain topics and clearly violates the spirit of the First Amendment, if not the letter of the law.
It goes far beyond conservative states yanking books about race and sex from public school libraries. Since 2021 in 40 state legislatures, 175 bills have been introduced or prefiled that target what teachers can say and what students can learn, often with severe penalties. Of those, 13 have become law in 11 states, and 106 are still under consideration. All told, 99 bills currently target K-12 public schools, 44 target higher education, and 59 include punishment for violators, according to a running tally kept by PEN America. In some instances, the proposed bills failed to become law. In other cases, the courts should declare them unconstitutional.
These bills include Floridas Dont Say Gay bill, which would restrict what teachers and students can talk about and allows for parents to file lawsuits. If the law goes into force, watch for lawsuits against schools that restrict the free speech rights of students to discuss things like sexuality, established by earlier Supreme Court rulings.
The new gag laws coincide with a similar barrage of bills that ostensibly target critical race theory, an idea that has percolated down from law schools to the broader public in recent years as a way to understand the pervasiveness of racism. The moral panic around critical race theory has morphed into a vast effort to restrict discussions of race, sex, American history and other topics that conservatives say are divisive. Several states have now passed these gag laws restricting what can be said in public schools, colleges and universities, and state agencies and institutions.
In passing laws that restrict speech, conservatives have adopted the language of harm that some liberals used in the past to restrict speech the idea that speech itself can cause an unacceptable harm, which has led to a proliferation of campus speech codes and the use of trigger warnings in college classrooms.
Now conservatives have used the idea of harmful speech to their own ends: An anti-critical-race-theory law in Tennessee passed last year, for instance, prohibits promoting the concept that an individual should feel discomfort, guilt, anguish or another form of psychological distress solely because of the individuals race or sex a measure aimed at avoiding the distress that students might feel when learning about racist or misogynist elements of American history. (Unmentioned, of course, is the potential discomfort felt by students who are fed a whitewashed version of American history.)
Link:
Opinion | America Has a Free Speech Problem - The New York Times
A Declaration of the Independence of Cyberspace
by John Perry Barlow
Governments of the Industrial World, you weary giants of flesh and steel, I come from Cyberspace, the new home of Mind. On behalf of the future, I ask you of the past to leave us alone. You are not welcome among us. You have no sovereignty where we gather.
We have no elected government, nor are we likely to have one, so I address you with no greater authority than that with which liberty itself always speaks. I declare the global social space we are building to be naturally independent of the tyrannies you seek to impose on us. You have no moral right to rule us nor do you possess any methods of enforcement we have true reason to fear.
Governments derive their just powers from the consent of the governed. You have neither solicited nor received ours. We did not invite you. You do not know us, nor do you know our world. Cyberspace does not lie within your borders. Do not think that you can build it, as though it were a public construction project. You cannot. It is an act of nature and it grows itself through our collective actions.
You have not engaged in our great and gathering conversation, nor did you create the wealth of our marketplaces. You do not know our culture, our ethics, or the unwritten codes that already provide our society more order than could be obtained by any of your impositions.
You claim there are problems among us that you need to solve. You use this claim as an excuse to invade our precincts. Many of these problems don't exist. Where there are real conflicts, where there are wrongs, we will identify them and address them by our means. We are forming our own Social Contract. This governance will arise according to the conditions of our world, not yours. Our world is different.
Cyberspace consists of transactions, relationships, and thought itself, arrayed like a standing wave in the web of our communications. Ours is a world that is both everywhere and nowhere, but it is not where bodies live.
We are creating a world that all may enter without privilege or prejudice accorded by race, economic power, military force, or station of birth.
We are creating a world where anyone, anywhere may express his or her beliefs, no matter how singular, without fear of being coerced into silence or conformity.
Your legal concepts of property, expression, identity, movement, and context do not apply to us. They are all based on matter, and there is no matter here.
Our identities have no bodies, so, unlike you, we cannot obtain order by physical coercion. We believe that from ethics, enlightened self-interest, and the commonweal, our governance will emerge. Our identities may be distributed across many of your jurisdictions. The only law that all our constituent cultures would generally recognize is the Golden Rule. We hope we will be able to build our particular solutions on that basis. But we cannot accept the solutions you are attempting to impose.
In the United States, you have today created a law, the Telecommunications Reform Act, which repudiates your own Constitution and insults the dreams of Jefferson, Washington, Mill, Madison, DeToqueville, and Brandeis. These dreams must now be born anew in us.
You are terrified of your own children, since they are natives in a world where you will always be immigrants. Because you fear them, you entrust your bureaucracies with the parental responsibilities you are too cowardly to confront yourselves. In our world, all the sentiments and expressions of humanity, from the debasing to the angelic, are parts of a seamless whole, the global conversation of bits. We cannot separate the air that chokes from the air upon which wings beat.
In China, Germany, France, Russia, Singapore, Italy and the United States, you are trying to ward off the virus of liberty by erecting guard posts at the frontiers of Cyberspace. These may keep out the contagion for a small time, but they will not work in a world that will soon be blanketed in bit-bearing media.
Your increasingly obsolete information industries would perpetuate themselves by proposing laws, in America and elsewhere, that claim to own speech itself throughout the world. These laws would declare ideas to be another industrial product, no more noble than pig iron. In our world, whatever the human mind may create can be reproduced and distributed infinitely at no cost. The global conveyance of thought no longer requires your factories to accomplish.
These increasingly hostile and colonial measures place us in the same position as those previous lovers of freedom and self-determination who had to reject the authorities of distant, uninformed powers. We must declare our virtual selves immune to your sovereignty, even as we continue to consent to your rule over our bodies. We will spread ourselves across the Planet so that no one can arrest our thoughts.
We will create a civilization of the Mind in Cyberspace. May it be more humane and fair than the world your governments have made before.
Davos, SwitzerlandFebruary 8, 1996
Link:
Our Constitution is Open, Futuristic, and Known for Its Vision. Our Constitution is … – Latest Tweet by – LatestLY
This Analysis Shows How Viral Fake Election News … – BuzzFeed News
How We Gathered the Data
BuzzFeed News used the content analysis tool BuzzSumo, which enables users to search for content by keyword, URL, time range, and social share counts. BuzzFeed News searched in BuzzSumo using keywords such as "Hillary Clinton" and "Donald Trump," as well as combinations such as "Trump and election" or "Clinton and emails" to see the top stories about these topics according to Facebook engagement. We also searched for known viral lies such as "Soros and voting machine."
In addition, created lists of the URLs of known fake news websites, of hyperpartisan sites on the right and on the left, and of the more than 100 pro-Trump sites run from Macedonia that were previously identified in BuzzFeed News reporting. We then looked for the top performing content on Facebook across all of these sites to find false stories about the election.
We conducted our searches in three-month segments beginning 9 months from election day. This broke down as February to April, May to July, and August to election day.
Even with the above approaches, it's entirely possible that we missed other big hits from fake news websites and hyperpartisan blogs.
To examine the performance of election content from mainstream sites, we created a list that included the websites of the New York Times, Washington Post, NBC News, USA Today, Politico, CNN, Wall Street Journal, CBS News, ABC News, New York Daily News, New York Post, BuzzFeed, Los Angeles Times, NPR, The Guardian, Vox, Business Insider, Huffington Post, and Fox News. We then searched for their top-performing election content in the same three-month segments as above.
It's important to note that Facebook engagement does not necessarily translate into traffic. This analysis was focused on how the best-performing fake news about the election compared with real news from major outlets on Facebook. It's entirely possible and likely that the mainstream sites received more traffic to their top-performing Facebook content than the fake news sites did. As as the Facebook spokesman noted, large news sites overall see more engagement on Facebook than fake news sites.
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This Analysis Shows How Viral Fake Election News ... - BuzzFeed News
Is That True? 4 Browser Extensions to Help You Spot Fake News
Fake news has become a pervasive problem on the internet. You find a news site or story online but you don't know if you can trust it. Is it true? Is it accurate? Is it reliable? Not even yourFacebook friendsknow how to tell the difference. But you can find out if a news site or a specific article is considered reliable and truthful, courtesy of the right browser plug-in.
Extensions like NewsGuard, TrustServista, Media Bias/Fact Check, and The Factual integrate into your browser and display grades, rankings, and reports to tell you more about the news sources you view. You can then better determine if the stories you read should be trusted.
(Credit: Lance Whitney)
NewsGuard(Opens in a new window)relies on a team of journalists who analyze more than 5,800 news websites in the US, each of which is evaluated and ranked on nine different criteria:
Does the site repeatedly publish false content?
Does it gather and present information responsibly?
Does it regularly correct or clarify errors?
Does it handle the difference between news and opinion responsibly?
Does it avoid deceptive headlines?
Does it disclose ownership and financing about itself?
Does it clearly label advertising?
Does it reveal who's in charge, including possible conflicts of interest?
Does it provide information about content creators?
Each criteria is given a certain weigh, or number of points, to determine the site's overall rating. A site earns a green rating if it meets basic standards of accuracy and accountability. A red rating means it fails to meet those minimum standards.
After NewsGuard is activated, an icon for the plug-in appears on your browser's toolbar. Open to a website that NewsGuard's team has analyzed, and the icon turns green or red, depending on the site's ranking. Click the icon to find out why the site earned its stripes. Clicking the link to view the full nutrition label serves up greater details that reveal the ownership, content, history, background, and credibility (or lack thereof) of the site. The label also lists the authors behind the report and the sources they used.
NewsGuard even works off-site. Conduct a web search using Google or Bing, and the extension's icon will appear next to any news source that appear in the results. Hover over the icon to view NewsGuard's analysis of the site. The service offers a free two-week trial, after which it costs $4.95 per month for Chrome(Opens in a new window) and Firefox(Opens in a new window) users. Those who use Microsoft Edge(Opens in a new window) can use the feature for free.
(Credit: Lance Whitney)
Using artificial intelligence and other analytics, TrustServista(Opens in a new window) tries to gauge the trustworthiness of a news article. Designed for Google Chrome (and Edge)(Opens in a new window), this extension analyzes an article and then delivers different types of feedback and metrics, including the context setting (the amount of factual information), the sentiment (negative, neutral, or positive), the veracity of the source (known publisher or named author) and the likelihood of the article being clickbait.
After installing the TrustServista extension, click its toolbar icon to analyze the news story open in your browser. The extension will display the name of the articles author, article type, context, sentiment, its clickbait potential, and its content quality score. (You may see a message telling you that the extension is currently processing the site and to try again in 30 seconds.)
Naturally, the lower the score, the less trustworthy the article is considered. Scroll down further to see more details and a list of keywords used in the article. TrustServista is free but limits you to 300 articles analyzed per month. For $2.99 a month, the limit is upped to 3,000 per month.
The Media Bias/Fact Check Resource(Opens in a new window), an independent website with a stated goal of promoting awareness of media bias and misinformation, offers its own browser extension that focuses on political bias. Instead of grading news sources based on specific criteria, the tool evaluates a site based on factual reporting, like how accurate and reliable the information is and how proper the sources for that information are.
Toward that end, the siteand its extensionuse human analysts and evaluators to examine and rate the bias of different news sources. The extension, available for Chrome(Opens in a new window), Edge(Opens in a new window), andFirefox(Opens in a new window), assigns rankings to news sites based on the analysis of bias. A site can receive any of the following grades:
L Left Bias
LC Left-Center Bias
C Center (Least Biased)
RC Right-Center Bias
R Right Bias
PS Pro-Science
CP Conspiracy-Pseudoscience
S Satire
Q Questionable Sources
After you install the MBFC extension, browse to a particular website. The toolbar icon changes its color and initial to indicate the bias ranking for that content. Click the icon, and a description pops up to explain the specific level of bias assigned to that site. Click the detailed report link for the news site and you'll see examples that explain why the site was evaluated with a certain bias. The report also includes a history and background of the site.
The Factual(Opens in a new window) offers a newsletter, website, mobile app, and Chrome extension aimed at helping people get factual news. Through an algorithm backed by cross-checking from human editors, the Factual evaluates more than 10,000 articles each day. The Chrome extension(Opens in a new window) rates articles based on quality, tone, and other factors so you can decide whether a story is worth your time, well-researched, isnt too opinionated, and is written by a knowledgeable reporter.
After installing the extension in Chrome or Microsoft Edge, browse to a news article. Click the Factuals toolbar icon to see its feedback on the story. A factual grade and a political bias are assigned based on the authors expertise, quality, tone, and quality of the sources. Hover over an info icon for each metric to see its definition. Clicking a link to show details reveals even more information about the specific story and rankings.
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Is That True? 4 Browser Extensions to Help You Spot Fake News
Fake news: How to spot misinformation : Life Kit : NPR
Fake news has consequences.
Back in 2016, before the term was even part of our national vocabulary, it threw the government of Twin Falls, Idaho, into chaos.
Rumors of a government cover-up involving child molestation and Syrian refugees swirled. They soon leaped from the fringes of the Internet to kitchen tables and the mainstream media.
"Members of the local government, the mayor, the city council members, local judges, the county prosecutor, they were basically inundated for months on end with threats," says Caitlin Dickerson, who covered the story for The New York Times. "Violent threats. Very visceral and descriptive threats from all over the world."
But the outrage was not based on facts. The details were blurred in some cases, completely fabricated in others, depending on the storyteller and their agenda.
It was a grave example of how misinformation can have a terrifying real-world impact. But falsehoods aren't hard to come by in today's information landscape.
Here are five tips to help you spot misinformation. (Or if you would rather listen, check out the Life Kit podcast here.)
1) Exercise skepticism
Take in any new information, whether it's the news or on social media or from a buddy at happy hour, with a bit of doubt. Expect the source to prove their work and show how they came to their conclusion. And try to compare information from a number of different outlets, even if you have a favorite.
2) Understand the misinformation landscape
Misinformation, as a concept, isn't new. But the social media platforms for engaging with it are constantly changing and increasing their influence in the media world. Those platforms have no financial obligation to tell the truth their business models depend on user engagement. Reducing your dependence on social media will be good for your news judgment (and your sleep).
3) Pay extra attention when reading about emotionally-charged and divisive topics
Misinformation is most effective on hot-button issues and immediate news. Ask yourself: Is this a complicated subject, something that's hitting an emotional trigger? Or is it a breaking news story where the facts aren't yet able to be assembled? If the answer is yes, then you need to be ultra-skeptical.
4) Investigate what you're reading or seeing
What does that skepticism look like in practice? It means asking some questions of what you're reading or seeing: Is the content paid for by a company or politician or other potentially biased source? Is there good evidence? And are the numbers presented in context?
(The News Literacy Project created an app to help people test and strengthen their media literacy skills.)
5) Yelling probably won't solve misinformation
It's important to value the truth, but correcting people is always delicate. If someone in your life is spreading objective falsehoods and you want to help, be humble. Don't assume bad intentions or stupidity, just meet the other person where they are and be curious think about opening with common ground and a question. Try to have the conversation in person or at least in a private online setting, like an email.
If you want more resources, Media Literacy Now is a good place to start.
See original here:
How fake news spreads like a real virus – Stanford University School of …
When it comes to real fake news, the kind of disinformation that Russia deployed during the 2016 elections, going viral isnt just a metaphor.
Using the tools for modelling the spread of infectious disease, cyber-risk researchers at Stanford Engineering are analyzing the spread of fake news much as if it were a strain of Ebola. We want to find the most effective way to cut the transmission chains, correct the information if possible and educate the most vulnerable targets, saysElisabeth Pat-Cornell, a professor of management science and engineering. She has long specialized in risk analysis and cybersecurity and is overseeing the research in collaboration with Travis I. Trammell, a doctoral candidate at Stanford. Here are some of the key learnings:
The researchers have adapted a model for understanding diseases that can infect a person more than once. It looks at how many people are susceptible to the disease or in this case, likely to believe a piece of fake news. It also looks at how many have been exposed to it, and how many are actually infected and believe the story; and how many people are likely to spread a piece of fake news.
Much like a virus, the researchers say that over time being exposed to multiple strains of fake news can wear down a persons resistance and make them increasingly susceptible. The more times a person is exposed to a piece of fake news, especially if it comes from an influential source, the more likely they are to become persuaded or infected.
The so-called power law' of social media, a well-documented pattern in social networks, holds that messages replicate most rapidly if they are targeted at relatively small numbers of influential people with large followings.
Researchers are also looking at the relative effectiveness of trolls versus bots. Trammell says bots, which are automated programs that masquerade as people, tend to be particularly good for spreading massive numbers of highly emotional messages with little informational content. Think here of a message with the image of Hillary Clinton behind bars and the words Lock Her Up! That kind of message will spread rapidly within the echo chambers populated by those who already agree with the basic sentiment. Bots have considerable power to inflame people who are already like-minded, though they can be easier to detect and block than trolls.
By contrast, trolls are typically real people who spread provocative stories and memes. Trolls can be better at persuading people who are less convinced and want more information.
Pat-Cornell and Trammell say there is considerable evidence that the elderly, the young and the lesser educated are particularly susceptible to fake news. But in the broadest sense it is partisans at the political extremes, whether liberal or conservative, who are most like to believe a false story in part because of confirmation bias the tendency in all of us to believe stories that reinforce our convictions and the stronger those convictions, the more powerfully the person feels the pull of confirmation bias.
Pat-Cornell and Trammell say that, much like ordinary crime, disinformation will never disappear. But by learning how it is propagated through social media, the researchers say its possible to fight back. Social media platforms could become much quicker at spotting suspect content. They could then attach warnings a form of inoculation or they could quarantine more of it.
The challenge, they say, is that protection has costs financial costs as well as reduced convenience and limitations on free expression. Pat-Cornell says the dangers of fake news should be analyzed as a strategic management risk similar to how we have traditionally analyzed the risks posed by cyberattacks aimed at disabling critical infrastructure. Its an issue of how we can best manage our resources in order to minimize the risk, she says. How much are you willing to spend, and what level of risk are we willing to accept?
Fake news is already a national security issue. But Pat-Cornell and Trammell predict that artificial intelligence will turbocharge fake news in the years ahead. AI will make it much easier to target people with fake news or deep-fake videos videos that appear real but have been fabricated in whole or in part that are finely tailored to what a susceptible viewer is likely to accept and perhaps spread. AI could also make it easy to create armies of more influential bots that appear to share a targets social background, hometown, personal interests or religious beliefs. Such kinds of hyper-targeting would make the messages much more persuasive. AI also shows great potential to counter this scourge by identifying fake content in all forms, but only time will tell who prevails in this new age arms race.
Related |Elisabeth Pat-Cornell, the Burt and Deedee McMurtry Professor in the School of Engineering.
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How fake news spreads like a real virus - Stanford University School of ...
Stem cell – Wikipedia
Undifferentiated biological cells that can differentiate into specialized cells
In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can differentiate into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type of cell in a cell lineage.[1] They are found in both embryonic and adult organisms, but they have slightly different properties in each. They are usually distinguished from progenitor cells, which cannot divide indefinitely, and precursor or blast cells, which are usually committed to differentiating into one cell type.
In mammals, roughly 50150 cells make up the inner cell mass during the blastocyst stage of embryonic development, around days 514. These have stem-cell capability. In vivo, they eventually differentiate into all of the body's cell types (making them pluripotent). This process starts with the differentiation into the three germ layers the ectoderm, mesoderm and endoderm at the gastrulation stage. However, when they are isolated and cultured in vitro, they can be kept in the stem-cell stage and are known as embryonic stem cells (ESCs).
Adult stem cells are found in a few select locations in the body, known as niches, such as those in the bone marrow or gonads. They exist to replenish rapidly lost cell types and are multipotent or unipotent, meaning they only differentiate into a few cell types or one type of cell. In mammals, they include, among others, hematopoietic stem cells, which replenish blood and immune cells, basal cells, which maintain the skin epithelium, and mesenchymal stem cells, which maintain bone, cartilage, muscle and fat cells. Adult stem cells are a small minority of cells; they are vastly outnumbered by the progenitor cells and terminally differentiated cells that they differentiate into.[1]
Research into stem cells grew out of findings by Canadian biologists Ernest McCulloch, James Till and Andrew J. Becker at the University of Toronto and the Ontario Cancer Institute in the 1960s.[2][3] As of 2016[update], the only established medical therapy using stem cells is hematopoietic stem cell transplantation,[4] first performed in 1958 by French oncologist Georges Math. Since 1998 however, it has been possible to culture and differentiate human embryonic stem cells (in stem-cell lines). The process of isolating these cells has been controversial, because it typically results in the destruction of the embryo. Sources for isolating ESCs have been restricted in some European countries and Canada, but others such as the UK and China have promoted the research.[5] Somatic cell nuclear transfer is a cloning method that can be used to create a cloned embryo for the use of its embryonic stem cells in stem cell therapy.[6] In 2006, a Japanese team led by Shinya Yamanaka discovered a method to convert mature body cells back into stem cells. These were termed induced pluripotent stem cells (iPSCs).[7]
The term stem cell was coined by Theodor Boveri and Valentin Haecker in late 19th century.[8] Pioneering works in theory of blood stem cell were conducted in the beginning of 20th century by Artur Pappenheim, Alexander Maximow, Franz Ernst Christian Neumann.[8]
The key properties of a stem cell were first defined by Ernest McCulloch and James Till at the University of Toronto and the Ontario Cancer Institute in the early 1960s. They discovered the blood-forming stem cell, the hematopoietic stem cell (HSC), through their pioneering work in mice. McCulloch and Till began a series of experiments in which bone marrow cells were injected into irradiated mice. They observed lumps in the spleens of the mice that were linearly proportional to the number of bone marrow cells injected. They hypothesized that each lump (colony) was a clone arising from a single marrow cell (stem cell). In subsequent work, McCulloch and Till, joined by graduate student Andrew John Becker and senior scientist Louis Siminovitch, confirmed that each lump did in fact arise from a single cell. Their results were published in Nature in 1963. In that same year, Siminovitch was a lead investigator for studies that found colony-forming cells were capable of self-renewal, which is a key defining property of stem cells that Till and McCulloch had theorized.[9]
The first therapy using stem cells was a bone marrow transplant performed by French oncologist Georges Math in 1958 on five workers at the Vina Nuclear Institute in Yugoslavia who had been affected by a criticality accident. The workers all survived.[10]
In 1981, embryonic stem (ES) cells were first isolated and successfully cultured using mouse blastocysts by British biologists Martin Evans and Matthew Kaufman. This allowed the formation of murine genetic models, a system in which the genes of mice are deleted or altered in order to study their function in pathology. By 1998, embryonic stem cells were first isolated by American biologist James Thomson, which made it possible to have new transplantation methods or various cell types for testing new treatments. In 2006, Shinya Yamanakas team in Kyoto, Japan converted fibroblasts into pluripotent stem cells by modifying the expression of only four genes. The feat represents the origin of induced pluripotent stem cells, known as iPS cells.[7]
In 2011, a female maned wolf, run over by a truck, underwent stem cell treatment at the Zoo Braslia, this being the first recorded case of the use of stem cells to heal injuries in a wild animal.[11][12]
The classical definition of a stem cell requires that it possesses two properties:
Two mechanisms ensure that a stem cell population is maintained (doesn't shrink in size):
1. Asymmetric cell division: a stem cell divides into one mother cell, which is identical to the original stem cell, and another daughter cell, which is differentiated.
When a stem cell self-renews, it divides and does not disrupt the undifferentiated state. This self-renewal demands control of cell cycle as well as upkeep of multipotency or pluripotency, which all depends on the stem cell.[13]
2. Stochastic differentiation: when one stem cell grows and divides into two differentiated daughter cells, another stem cell undergoes mitosis and produces two stem cells identical to the original.
Stem cells use telomerase, a protein that restores telomeres, to protect their DNA and extend their cell division limit (the Hayflick limit).[14]
Potency specifies the differentiation potential (the potential to differentiate into different cell types) of the stem cell.[15]
In practice, stem cells are identified by whether they can regenerate tissue. For example, the defining test for bone marrow or hematopoietic stem cells (HSCs) is the ability to transplant the cells and save an individual without HSCs. This demonstrates that the cells can produce new blood cells over a long term. It should also be possible to isolate stem cells from the transplanted individual, which can themselves be transplanted into another individual without HSCs, demonstrating that the stem cell was able to self-renew.
Properties of stem cells can be illustrated in vitro, using methods such as clonogenic assays, in which single cells are assessed for their ability to differentiate and self-renew.[18][19] Stem cells can also be isolated by their possession of a distinctive set of cell surface markers. However, in vitro culture conditions can alter the behavior of cells, making it unclear whether the cells shall behave in a similar manner in vivo. There is considerable debate as to whether some proposed adult cell populations are truly stem cells.[20]
Embryonic stem cells (ESCs) are the cells of the inner cell mass of a blastocyst, formed prior to implantation in the uterus.[21] In human embryonic development the blastocyst stage is reached 45 days after fertilization, at which time it consists of 50150 cells. ESCs are pluripotent and give rise during development to all derivatives of the three germ layers: ectoderm, endoderm and mesoderm. In other words, they can develop into each of the more than 200 cell types of the adult body when given sufficient and necessary stimulation for a specific cell type. They do not contribute to the extraembryonic membranes or to the placenta.
During embryonic development the cells of the inner cell mass continuously divide and become more specialized. For example, a portion of the ectoderm in the dorsal part of the embryo specializes as 'neurectoderm', which will become the future central nervous system.[22] Later in development, neurulation causes the neurectoderm to form the neural tube. At the neural tube stage, the anterior portion undergoes encephalization to generate or 'pattern' the basic form of the brain. At this stage of development, the principal cell type of the CNS is considered a neural stem cell.
The neural stem cells self-renew and at some point transition into radial glial progenitor cells (RGPs). Early-formed RGPs self-renew by symmetrical division to form a reservoir group of progenitor cells. These cells transition to a neurogenic state and start to divide asymmetrically to produce a large diversity of many different neuron types, each with unique gene expression, morphological, and functional characteristics. The process of generating neurons from radial glial cells is called neurogenesis. The radial glial cell, has a distinctive bipolar morphology with highly elongated processes spanning the thickness of the neural tube wall. It shares some glial characteristics, most notably the expression of glial fibrillary acidic protein (GFAP).[23][24] The radial glial cell is the primary neural stem cell of the developing vertebrate CNS, and its cell body resides in the ventricular zone, adjacent to the developing ventricular system. Neural stem cells are committed to the neuronal lineages (neurons, astrocytes, and oligodendrocytes), and thus their potency is restricted.[22]
Nearly all research to date has made use of mouse embryonic stem cells (mES) or human embryonic stem cells (hES) derived from the early inner cell mass. Both have the essential stem cell characteristics, yet they require very different environments in order to maintain an undifferentiated state. Mouse ES cells are grown on a layer of gelatin as an extracellular matrix (for support) and require the presence of leukemia inhibitory factor (LIF) in serum media. A drug cocktail containing inhibitors to GSK3B and the MAPK/ERK pathway, called 2i, has also been shown to maintain pluripotency in stem cell culture.[25] Human ESCs are grown on a feeder layer of mouse embryonic fibroblasts and require the presence of basic fibroblast growth factor (bFGF or FGF-2).[26] Without optimal culture conditions or genetic manipulation,[27] embryonic stem cells will rapidly differentiate.
A human embryonic stem cell is also defined by the expression of several transcription factors and cell surface proteins. The transcription factors Oct-4, Nanog, and Sox2 form the core regulatory network that ensures the suppression of genes that lead to differentiation and the maintenance of pluripotency.[28] The cell surface antigens most commonly used to identify hES cells are the glycolipids stage specific embryonic antigen 3 and 4, and the keratan sulfate antigens Tra-1-60 and Tra-1-81. The molecular definition of a stem cell includes many more proteins and continues to be a topic of research.[29]
By using human embryonic stem cells to produce specialized cells like nerve cells or heart cells in the lab, scientists can gain access to adult human cells without taking tissue from patients. They can then study these specialized adult cells in detail to try to discern complications of diseases, or to study cell reactions to proposed new drugs.
Because of their combined abilities of unlimited expansion and pluripotency, embryonic stem cells remain a theoretically potential source for regenerative medicine and tissue replacement after injury or disease.,[30] however, there are currently no approved treatments using ES cells. The first human trial was approved by the US Food and Drug Administration in January 2009.[31] However, the human trial was not initiated until October 13, 2010 in Atlanta for spinal cord injury research. On November 14, 2011 the company conducting the trial (Geron Corporation) announced that it will discontinue further development of its stem cell programs.[32] Differentiating ES cells into usable cells while avoiding transplant rejection are just a few of the hurdles that embryonic stem cell researchers still face.[33] Embryonic stem cells, being pluripotent, require specific signals for correct differentiation if injected directly into another body, ES cells will differentiate into many different types of cells, causing a teratoma. Ethical considerations regarding the use of unborn human tissue are another reason for the lack of approved treatments using embryonic stem cells. Many nations currently have moratoria or limitations on either human ES cell research or the production of new human ES cell lines.
Human embryonic stem cell colony on mouse embryonic fibroblast feeder layer
Mesenchymal stem cells (MSC) or mesenchymal stromal cells, also known as medicinal signaling cells are known to be multipotent, which can be found in adult tissues, for example, in the muscle, liver, bone marrow and adipose tissue. Mesenchymal stem cells usually function as structural support in various organs as mentioned above, and control the movement of substances. MSC can differentiate into numerous cell categories as an illustration of adipocytes, osteocytes, and chondrocytes, derived by the mesodermal layer.[34] Where the mesoderm layer provides an increase to the bodys skeletal elements, such as relating to the cartilage or bone. The term meso means middle, infusion originated from the Greek, signifying that mesenchymal cells are able to range and travel in early embryonic growth among the ectodermal and endodermal layers. This mechanism helps with space-filling thus, key for repairing wounds in adult organisms that have to do with mesenchymal cells in the dermis (skin), bone, or muscle.[35]
Mesenchymal stem cells are known to be essential for regenerative medicine. They are broadly studied in clinical trials. Since they are easily isolated and obtain high yield, high plasticity, which makes able to facilitate inflammation and encourage cell growth, cell differentiation, and restoring tissue derived from immunomodulation and immunosuppression. MSC comes from the bone marrow, which requires an aggressive procedure when it comes to isolating the quantity and quality of the isolated cell, and it varies by how old the donor. When comparing the rates of MSC in the bone marrow aspirates and bone marrow stroma, the aspirates tend to have lower rates of MSC than the stroma. MSC are known to be heterogeneous, and they express a high level of pluripotent markers when compared to other types of stem cells, such as embryonic stem cells.[34] MSCs injection leads to wound healing primarily through stimulation of angiogenesis.[36]
Embryonic stem cells (ESCs) have the ability to divide indefinitely while keeping their pluripotency, which is made possible through specialized mechanisms of cell cycle control.[37] Compared to proliferating somatic cells, ESCs have unique cell cycle characteristicssuch as rapid cell division caused by shortened G1 phase, absent G0 phase, and modifications in cell cycle checkpointswhich leaves the cells mostly in S phase at any given time.[37][38] ESCs rapid division is demonstrated by their short doubling time, which ranges from 8 to 10 hours, whereas somatic cells have doubling time of approximately 20 hours or longer.[39] As cells differentiate, these properties change: G1 and G2 phases lengthen, leading to longer cell division cycles. This suggests that a specific cell cycle structure may contribute to the establishment of pluripotency.[37]
Particularly because G1 phase is the phase in which cells have increased sensitivity to differentiation, shortened G1 is one of the key characteristics of ESCs and plays an important role in maintaining undifferentiated phenotype. Although the exact molecular mechanism remains only partially understood, several studies have shown insight on how ESCs progress through G1and potentially other phasesso rapidly.[38]
The cell cycle is regulated by complex network of cyclins, cyclin-dependent kinases (Cdk), cyclin-dependent kinase inhibitors (Cdkn), pocket proteins of the retinoblastoma (Rb) family, and other accessory factors.[39] Foundational insight into the distinctive regulation of ESC cell cycle was gained by studies on mouse ESCs (mESCs).[38] mESCs showed a cell cycle with highly abbreviated G1 phase, which enabled cells to rapidly alternate between M phase and S phase. In a somatic cell cycle, oscillatory activity of Cyclin-Cdk complexes is observed in sequential action, which controls crucial regulators of the cell cycle to induce unidirectional transitions between phases: Cyclin D and Cdk4/6 are active in the G1 phase, while Cyclin E and Cdk2 are active during the late G1 phase and S phase; and Cyclin A and Cdk2 are active in the S phase and G2, while Cyclin B and Cdk1 are active in G2 and M phase.[39] However, in mESCs, this typically ordered and oscillatory activity of Cyclin-Cdk complexes is absent. Rather, the Cyclin E/Cdk2 complex is constitutively active throughout the cycle, keeping retinoblastoma protein (pRb) hyperphosphorylated and thus inactive. This allows for direct transition from M phase to the late G1 phase, leading to absence of D-type cyclins and therefore a shortened G1 phase.[38] Cdk2 activity is crucial for both cell cycle regulation and cell-fate decisions in mESCs; downregulation of Cdk2 activity prolongs G1 phase progression, establishes a somatic cell-like cell cycle, and induces expression of differentiation markers.[40]
In human ESCs (hESCs), the duration of G1 is dramatically shortened. This has been attributed to high mRNA levels of G1-related Cyclin D2 and Cdk4 genes and low levels of cell cycle regulatory proteins that inhibit cell cycle progression at G1, such as p21CipP1, p27Kip1, and p57Kip2.[37][41] Furthermore, regulators of Cdk4 and Cdk6 activity, such as members of the Ink family of inhibitors (p15, p16, p18, and p19), are expressed at low levels or not at all. Thus, similar to mESCs, hESCs show high Cdk activity, with Cdk2 exhibiting the highest kinase activity. Also similar to mESCs, hESCs demonstrate the importance of Cdk2 in G1 phase regulation by showing that G1 to S transition is delayed when Cdk2 activity is inhibited and G1 is arrest when Cdk2 is knocked down.[37] However unlike mESCs, hESCs have a functional G1 phase. hESCs show that the activities of Cyclin E/Cdk2 and Cyclin A/Cdk2 complexes are cell cycle-dependent and the Rb checkpoint in G1 is functional.[39]
ESCs are also characterized by G1 checkpoint non-functionality, even though the G1 checkpoint is crucial for maintaining genomic stability. In response to DNA damage, ESCs do not stop in G1 to repair DNA damages but instead, depend on S and G2/M checkpoints or undergo apoptosis. The absence of G1 checkpoint in ESCs allows for the removal of cells with damaged DNA, hence avoiding potential mutations from inaccurate DNA repair.[37] Consistent with this idea, ESCs are hypersensitive to DNA damage to minimize mutations passed onto the next generation.[39]
The primitive stem cells located in the organs of fetuses are referred to as fetal stem cells.[42]
There are two types of fetal stem cells:
Adult stem cells, also called somatic (from Greek , "of the body") stem cells, are stem cells which maintain and repair the tissue in which they are found.[44] They can be found in children, as well as adults.[45]
There are three known accessible sources of autologous adult stem cells in humans:
Stem cells can also be taken from umbilical cord blood just after birth. Of all stem cell types, autologous harvesting involves the least risk. By definition, autologous cells are obtained from one's own body, just as one may bank their own blood for elective surgical procedures.[citation needed]
Pluripotent adult stem cells are rare and generally small in number, but they can be found in umbilical cord blood and other tissues.[49] Bone marrow is a rich source of adult stem cells,[50] which have been used in treating several conditions including liver cirrhosis,[51] chronic limb ischemia[52] and endstage heart failure.[53] The quantity of bone marrow stem cells declines with age and is greater in males than females during reproductive years.[54] Much adult stem cell research to date has aimed to characterize their potency and self-renewal capabilities.[55] DNA damage accumulates with age in both stem cells and the cells that comprise the stem cell environment. This accumulation is considered to be responsible, at least in part, for increasing stem cell dysfunction with aging (see DNA damage theory of aging).[56]
Most adult stem cells are lineage-restricted (multipotent) and are generally referred to by their tissue origin (mesenchymal stem cell, adipose-derived stem cell, endothelial stem cell, dental pulp stem cell, etc.).[57][58] Muse cells (multi-lineage differentiating stress enduring cells) are a recently discovered pluripotent stem cell type found in multiple adult tissues, including adipose, dermal fibroblasts, and bone marrow. While rare, muse cells are identifiable by their expression of SSEA-3, a marker for undifferentiated stem cells, and general mesenchymal stem cells markers such as CD90, CD105. When subjected to single cell suspension culture, the cells will generate clusters that are similar to embryoid bodies in morphology as well as gene expression, including canonical pluripotency markers Oct4, Sox2, and Nanog.[59]
Adult stem cell treatments have been successfully used for many years to treat leukemia and related bone/blood cancers through bone marrow transplants.[60] Adult stem cells are also used in veterinary medicine to treat tendon and ligament injuries in horses.[61]
The use of adult stem cells in research and therapy is not as controversial as the use of embryonic stem cells, because the production of adult stem cells does not require the destruction of an embryo. Additionally, in instances where adult stem cells are obtained from the intended recipient (an autograft), the risk of rejection is essentially non-existent. Consequently, more US government funding is being provided for adult stem cell research.[62]
With the increasing demand of human adult stem cells for both research and clinical purposes (typically 15 million cells per kg of body weight are required per treatment) it becomes of utmost importance to bridge the gap between the need to expand the cells in vitro and the capability of harnessing the factors underlying replicative senescence. Adult stem cells are known to have a limited lifespan in vitro and to enter replicative senescence almost undetectably upon starting in vitro culturing.[63]
Also called perinatal stem cells, these multipotent stem cells are found in amniotic fluid and umbilical cord blood. These stem cells are very active, expand extensively without feeders and are not tumorigenic. Amniotic stem cells are multipotent and can differentiate in cells of adipogenic, osteogenic, myogenic, endothelial, hepatic and also neuronal lines.[64]Amniotic stem cells are a topic of active research.
Use of stem cells from amniotic fluid overcomes the ethical objections to using human embryos as a source of cells. Roman Catholic teaching forbids the use of embryonic stem cells in experimentation; accordingly, the Vatican newspaper "Osservatore Romano" called amniotic stem cells "the future of medicine".[65]
It is possible to collect amniotic stem cells for donors or for autologous use: the first US amniotic stem cells bank[66][67] was opened in 2009 in Medford, MA, by Biocell Center Corporation[68][69][70] and collaborates with various hospitals and universities all over the world.[71]
Adult stem cells have limitations with their potency; unlike embryonic stem cells (ESCs), they are not able to differentiate into cells from all three germ layers. As such, they are deemed multipotent.
However, reprogramming allows for the creation of pluripotent cells, induced pluripotent stem cells (iPSCs), from adult cells. These are not adult stem cells, but somatic cells (e.g. epithelial cells) reprogrammed to give rise to cells with pluripotent capabilities. Using genetic reprogramming with protein transcription factors, pluripotent stem cells with ESC-like capabilities have been derived.[72][73][74] The first demonstration of induced pluripotent stem cells was conducted by Shinya Yamanaka and his colleagues at Kyoto University.[75] They used the transcription factors Oct3/4, Sox2, c-Myc, and Klf4 to reprogram mouse fibroblast cells into pluripotent cells.[72][76] Subsequent work used these factors to induce pluripotency in human fibroblast cells.[77] Junying Yu, James Thomson, and their colleagues at the University of WisconsinMadison used a different set of factors, Oct4, Sox2, Nanog and Lin28, and carried out their experiments using cells from human foreskin.[72][78] However, they were able to replicate Yamanaka's finding that inducing pluripotency in human cells was possible.
Induced pluripotent stem cells differ from embryonic stem cells. They share many similar properties, such as pluripotency and differentiation potential, the expression of pluripotency genes, epigenetic patterns, embryoid body and teratoma formation, and viable chimera formation,[75][76] but there are many differences within these properties. The chromatin of iPSCs appears to be more "closed" or methylated than that of ESCs.[75][76] Similarly, the gene expression pattern between ESCs and iPSCs, or even iPSCs sourced from different origins.[75] There are thus questions about the "completeness" of reprogramming and the somatic memory of induced pluripotent stem cells. Despite this, inducing somatic cells to be pluripotent appears to be viable.
As a result of the success of these experiments, Ian Wilmut, who helped create the first cloned animal Dolly the Sheep, has announced that he will abandon somatic cell nuclear transfer as an avenue of research.[79]
IPSCs has helped the field of medicine significantly by finding numerous ways to cure diseases. Since human IPSCc has given the advantage to make in vitro models to study toxins and pathogenesis.[80]
Furthermore, induced pluripotent stem cells provide several therapeutic advantages. Like ESCs, they are pluripotent. They thus have great differentiation potential; theoretically, they could produce any cell within the human body (if reprogramming to pluripotency was "complete").[75] Moreover, unlike ESCs, they potentially could allow doctors to create a pluripotent stem cell line for each individual patient.[81] Frozen blood samples can be used as a valuable source of induced pluripotent stem cells.[82] Patient specific stem cells allow for the screening for side effects before drug treatment, as well as the reduced risk of transplantation rejection.[81] Despite their current limited use therapeutically, iPSCs hold great potential for future use in medical treatment and research.
The key factors controlling the cell cycle also regulate pluripotency. Thus, manipulation of relevant genes can maintain pluripotency and reprogram somatic cells to an induced pluripotent state.[39] However, reprogramming of somatic cells is often low in efficiency and considered stochastic.[83]
With the idea that a more rapid cell cycle is a key component of pluripotency, reprogramming efficiency can be improved. Methods for improving pluripotency through manipulation of cell cycle regulators include: overexpression of Cyclin D/Cdk4, phosphorylation of Sox2 at S39 and S253, overexpression of Cyclin A and Cyclin E, knockdown of Rb, and knockdown of members of the Cip/Kip family or the Ink family.[39] Furthermore, reprogramming efficiency is correlated with the number of cell divisions happened during the stochastic phase, which is suggested by the growing inefficiency of reprogramming of older or slow diving cells.[84]
Lineage is an important procedure to analyze developing embryos. Since cell lineages shows the relationship between cells at each division. This helps in analyzing stem cell lineages along the way which helps recognize stem cell effectiveness, lifespan, and other factors. With the technique of cell lineage mutant genes can be analyzed in stem cell clones that can help in genetic pathways. These pathways can regulate how the stem cell perform.[85]
To ensure self-renewal, stem cells undergo two types of cell division (see Stem cell division and differentiation diagram). Symmetric division gives rise to two identical daughter cells both endowed with stem cell properties. Asymmetric division, on the other hand, produces only one stem cell and a progenitor cell with limited self-renewal potential. Progenitors can go through several rounds of cell division before terminally differentiating into a mature cell. It is possible that the molecular distinction between symmetric and asymmetric divisions lies in differential segregation of cell membrane proteins (such as receptors) between the daughter cells.[86]
An alternative theory is that stem cells remain undifferentiated due to environmental cues in their particular niche. Stem cells differentiate when they leave that niche or no longer receive those signals. Studies in Drosophila germarium have identified the signals decapentaplegic and adherens junctions that prevent germarium stem cells from differentiating.[87][88]
Stem cell therapy is the use of stem cells to treat or prevent a disease or condition. Bone marrow transplant is a form of stem cell therapy that has been used for many years because it has proven to be effective in clinical trials.[89][90]
Stem cell implantation may help in strengthening the left-ventricle of the heart, as well as retaining the heart tissue to patients who have suffered from heart attacks in the past.[91]
Stem cell treatments may lower symptoms of the disease or condition that is being treated. The lowering of symptoms may allow patients to reduce the drug intake of the disease or condition. Stem cell treatment may also provide knowledge for society to further stem cell understanding and future treatments.[92] The physicians' creed would be to do no injury, and stem cells make that simpler than ever before. Surgical processes by their character are harmful. Tissue has to be dropped as a way to reach a successful outcome. One may prevent the dangers of surgical interventions using stem cells. Additionally, there's a possibility of disease, and whether the procedure fails, further surgery may be required. Risks associated with anesthesia can also be eliminated with stem cells.[93] On top of that, stem cells have been harvested from the patient's body and redeployed in which they're wanted. Since they come from the patients own body, this is referred to as an autologous treatment. Autologous remedies are thought to be the safest because there's likely zero probability of donor substance rejection.
Stem cell treatments may require immunosuppression because of a requirement for radiation before the transplant to remove the person's previous cells, or because the patient's immune system may target the stem cells. One approach to avoid the second possibility is to use stem cells from the same patient who is being treated.
Pluripotency in certain stem cells could also make it difficult to obtain a specific cell type. It is also difficult to obtain the exact cell type needed, because not all cells in a population differentiate uniformly. Undifferentiated cells can create tissues other than desired types.[94]
Some stem cells form tumors after transplantation;[95] pluripotency is linked to tumor formation especially in embryonic stem cells, fetal proper stem cells, induced pluripotent stem cells. Fetal proper stem cells form tumors despite multipotency.[96]
Ethical concerns are also raised about the practice of using or researching embryonic stem cells. Harvesting cells from the blastocyst result in the death of the blastocyst. The concern is whether or not the blastocyst should be considered as a human life.[97] The debate on this issue is mainly a philosophical one, not a scientific one.
Stem cell tourism is the industry in which patients (and sometimes their families) travel to another jurisdiction, to obtain stem cell procedures which are not approved but which are advertised on the Internet as proven cures.[98]
The United States, in recent years[when?], has had an explosion of "stem cell clinics".[99] Stem cell procedures are highly profitable for clinics. The advertising sounds authoritative but the efficacy and safety of the procedures is unproven. Patients sometimes experience complications, such as spinal tumors[100] and death. The high expense can also lead to financial ruin.[100] According to researchers, there is a need to educate the public, patients, and doctors about this issue.[101]
According to the International Society for Stem Cell Research, the largest academic organization that advocates for stem cell research, stem cell therapies are under development and cannot yet be said to be proven.[102][103] Doctors should inform patients that clinical trials continue to investigate whether these therapies are safe and effective but that unethical clinics present them as proven.[104]
Some of the fundamental patents covering human embryonic stem cells are owned by the Wisconsin Alumni Research Foundation (WARF) they are patents 5,843,780, 6,200,806, and 7,029,913 invented by James A. Thomson. WARF does not enforce these patents against academic scientists, but does enforce them against companies.[105]
In 2006, a request for the US Patent and Trademark Office (USPTO) to re-examine the three patents was filed by the Public Patent Foundation on behalf of its client, the non-profit patent-watchdog group Consumer Watchdog (formerly the Foundation for Taxpayer and Consumer Rights).[105] In the re-examination process, which involves several rounds of discussion between the USPTO and the parties, the USPTO initially agreed with Consumer Watchdog and rejected all the claims in all three patents,[106] however in response, WARF amended the claims of all three patents to make them more narrow, and in 2008 the USPTO found the amended claims in all three patents to be patentable. The decision on one of the patents (7,029,913) was appealable, while the decisions on the other two were not.[107][108] Consumer Watchdog appealed the granting of the '913 patent to the USPTO's Board of Patent Appeals and Interferences (BPAI) which granted the appeal, and in 2010 the BPAI decided that the amended claims of the '913 patent were not patentable.[109] However, WARF was able to re-open prosecution of the case and did so, amending the claims of the '913 patent again to make them more narrow, and in January 2013 the amended claims were allowed.[110]
In July 2013, Consumer Watchdog announced that it would appeal the decision to allow the claims of the '913 patent to the US Court of Appeals for the Federal Circuit (CAFC), the federal appeals court that hears patent cases.[111] At a hearing in December 2013, the CAFC raised the question of whether Consumer Watchdog had legal standing to appeal; the case could not proceed until that issue was resolved.[112]
Diseases and conditions where stem cell treatment is being investigated include:
Research is underway to develop various sources for stem cells, and to apply stem cell treatments for neurodegenerative diseases and conditions, diabetes, heart disease, and other conditions.[132] Research is also underway in generating organoids using stem cells, which would allow for further understanding of human development, organogenesis, and modeling of human diseases.[133]
In more recent years, with the ability of scientists to isolate and culture embryonic stem cells, and with scientists' growing ability to create stem cells using somatic cell nuclear transfer and techniques to create induced pluripotent stem cells, controversy has crept in, both related to abortion politics and to human cloning.[citation needed]
Hepatotoxicity and drug-induced liver injury account for a substantial number of failures of new drugs in development and market withdrawal, highlighting the need for screening assays such as stem cell-derived hepatocyte-like cells, that are capable of detecting toxicity early in the drug development process.[134]
In August 2021, researchers in the Princess Margaret Cancer Centre at the University Health Network published their discovery of a dormancy mechanism in key stem cells which could help develop cancer treatments in the future.[135]
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Types of Stem Cell and Bone Marrow Transplants – American Cancer Society
Stem cell transplants are used to give back stem cells when the bone marrow has been destroyed by disease, chemotherapy (chemo), or radiation. Depending on where the stem cells come from, the transplant procedure may be called:
They can all be called hematopoietic stem cell transplants.
In a typical stem cell transplant for cancer, very high doses of chemo are used, sometimes along with radiation therapy, to try to kill all the cancer cells. This treatment also kills the stem cells in the bone marrow. This is called myeloablation or myeloablative therapy. Soon after treatment, stem cells are given (transplanted) to replace those that were destroyed. The replacement stem cells are given into a vein, much like ablood transfusion. The goal is that over time, the transplanted cells settle in the bone marrow, begin to grow and make healthy blood cells. This process is called engraftment.
There are 2 main types of transplants. They are named based on who donates the stem cells.
In this type of transplant, the first step is to remove or harvest your own stem cells. Your stem cells are removed from either your bone marrow or your blood, and then frozen. (You can learn more about this process at Whats It Like to Donate Stem Cells?) After you get high doses of chemo and/or radiation as your myeloablative therapy, the stem cells are thawed and given back to you.
Benefits of autologous stem cell transplant: One advantage of autologous stem cell transplant is that youre getting your own cells back. When you get your own stem cells back, you dont have to worry about them (called the engrafted cells or the graft) being rejected by your body.
Risks of autologous stem cell transplant: The grafts can still fail, which means the transplanted stem cells dont go into the bone marrow and make blood cells like they should. Also, autologous transplants cant produce the graft-versus-cancer effect. A possible disadvantage of an autologous transplant is that cancer cells might be collected along with the stem cells and then later put back into your body. Another disadvantage is that your immune system is the same as it was before your transplant. This means the cancer cells were able to escape attack from your immune system before, and may be able to do so again.
This kind of transplant is mainly used to treat certain leukemias, lymphomas, and multiple myeloma. Its sometimes used for other cancers, like testicular cancer and neuroblastoma, and certain cancers in children. Doctors can use autologous transplants for other diseases, too, like systemic sclerosis, multiple sclerosis (MS), and systemic lupus erythematosis (lupus).
To help prevent any remaining cancer cells from being transplanted along with stem cells, some centers treat the stem cells before theyre given back to the patient. This may be called purging. While this might work for some patients, there haven't been enough studies yet to know if this is really a benefit. A possible downside of purging is that some normal stem cells can be lost during this process. This may cause your body to take longer to start making normal blood cells, and you might have very low and unsafe levels of white blood cells or platelets for a longer time. This could increase the risk of infections or bleeding problems.
Another treatment to help kill cancer cells that might be in the returned stem cells involves giving anti-cancer drugs after the transplant. The stem cells are not treated. After transplant, the patient gets anti-cancer drugs to get rid of any cancer cells that may be in the body. This is called in vivo purging. For instance, lenalidomide (Revlimid) may be used in this way for multiple myeloma. The need to remove cancer cells from transplanted stem cells or transplant patients and the best way to do it continues to be researched.
Doing 2 autologous transplants in a row is known as a tandem transplant or a double autologous transplant. In this type of transplant, the patient gets 2 courses of high-dose chemo as myeloablative therapy, each followed by a transplant of their own stem cells. All of the stem cells needed are collected before the first high-dose chemo treatment, and half of them are used for each transplant. Usually, the 2 courses of chemo are given within 6 months. The second one is given after the patient recovers from the first one.
Tandem transplants have become the standard of care for certain cancers. High-risk types of the childhood cancer neuroblastoma and adult multiple myeloma are cancers where tandem transplants seem to show good results. But doctors dont always agree that these are really better than a single transplant for certain cancers. Because this treatment involves 2 transplants, the risk of serious outcomes is higher than for a single transplant.
Sometimes an autologous transplant followed by an allogeneic transplant might also be called a tandem transplant. (See Mini-transplants below.)
Allogeneic stem cell transplants use donor stem cells. In the most common type of allogeneic transplant, the stem cells come from a donor whose tissue type closely matches yours. (This is discussed in Matching patients and donors.) The best donor is a close family member, usually a brother or sister. If you dont have a good match in your family, a donor might be found in the general public through a national registry. This is sometimes called a MUD (matched unrelated donor) transplant. Transplants with a MUD are usually riskier than those with a relative who is a good match.
An allogeneic transplant works about the same way as an autologous transplant. Stem cells are collected from the donor and stored or frozen. After you get high doses of chemo and/or radiation as your myeloablative therapy, the donor's stem cells are thawed and given to you.
Blood taken from the placenta and umbilical cord of newborns is a type of allogeneic transplant. This small volume of cord blood has a high number of stem cells that tend to multiply quickly. Cord blood transplants are done for both adults and children. By 2017, an estimated 700,000 units (batches) of cord blood had been donated for public use. And, even more have been collected for private use. In some studies, the risk of a cancer not going away or coming back after a cord blood transplant was less than after an unrelated donor transplant.
Benefits of allogeneic stem cell transplant: The donor stem cells make their own immune cells, which could help kill any cancer cells that remain after high-dose treatment. This is called the graft-versus-cancer or graft-versus-tumor effect. Other advantages are that the donor can often be asked to donate more stem cells or even white blood cells if needed, and stem cells from healthy donors are free of cancer cells.
Risks of allogeneic stem cell transplants: The transplant, or graft, might not take that is, the transplanted donor stem cells could die or be destroyed by the patients body before settling in the bone marrow. Another risk is that the immune cells from the donor may not just attack the cancer cells they could attack healthy cells in the patients body. This is called graft-versus-host disease. There is also a very small risk of certain infections from the donor cells, even though donors are tested before they donate. A higher risk comes from infections you had previously, and which your immune system has had under control. These infections may surface after allogeneic transplant because your immune system is held in check (suppressed) by medicines called immunosuppressive drugs. Such infections can cause serious problems and even death.
Allogeneic transplant is most often used to treat certain types of leukemia, lymphomas, multiple myeloma, myelodysplastic syndrome, and other bone marrow disorders such as aplastic anemia.
For some people, age or certain health conditions make it more risky to do myeloablative therapy that wipes out all of their bone marrow before a transplant. For those people, doctors can use a type of allogeneic transplant thats sometimes called a mini-transplant. Your doctor might refer to it as a non-myeloablative transplant or mention reduced-intensity conditioning (RIC). Patients getting a mini transplant typically get lower doses of chemo and/or radiation than if they were getting a standard myeloablative transplant. The goal in the mini-transplant is to kill some of the cancer cells (which will also kill some of the bone marrow), and suppress the immune system just enough to allow donor stem cells to settle in the bone marrow.
Unlike the standard allogeneic transplant, cells from both the donor and the patient exist together in the patients body for some time after a mini-transplant. But slowly, over the course of months, the donor cells take over the bone marrow and replace the patients own bone marrow cells. These new cells can then develop an immune response to the cancer and help kill off the patients cancer cells the graft-versus-cancer effect.
One advantage of a mini-transplant is that it uses lower doses of chemo and/or radiation. And because the stem cells arent all killed, blood cell counts dont drop as low while waiting for the new stem cells to start making normal blood cells. This makes it especially useful for older patients and those with other health problems. Rarely, it may be used in patients who have already had a transplant.
Mini-transplants treat some diseases better than others. They may not work well for patients with a lot of cancer in their body or people with fast-growing cancers. Also, although there might be fewer side effects from chemo and radiation than those from a standard allogeneic transplant, the risk of graft-versus-host disease is the same. Some studies have shown that for some cancers and some other blood conditions, both adults and children can have the same kinds of results with a mini-transplant as compared to a standard transplant.
This is a special kind of allogeneic transplant that can only be used when the patient has an identical sibling (twin or triplet) someone who has the exact same tissue type. An advantage of syngeneic stem cell transplant is that graft-versus-host disease will not be a problem. Also, there are no cancer cells in the transplanted stem cells, as there might be in an autologous transplant.
A disadvantage is that because the new immune system is so much like the recipients immune system, theres no graft-versus-cancer effect. Every effort must be made to destroy all the cancer cells before the transplant is done to help keep the cancer from coming back.
Improvements have been made in the use of family members as donors. This kind of transplant is called ahalf-match (haploidentical) transplant for people who dont have fully matching or identical family member. This can be another option to consider, along with cord blood transplant and matched unrelated donor (MUD) transplant.
If possible, it is very important that the donor and recipient are a close tissue match to avoid graft rejection. Graft rejection happens when the recipients immune system recognizes the donor cells as foreign and tries to destroy them as it would a bacteria or virus. Graft rejection can lead to graft failure, but its rare when the donor and recipient are well matched.
A more common problem is that when the donor stem cells make their own immune cells, the new cells may see the patients cells as foreign and attack their new home. This is called graft-versus-host disease. (See Stem Cell Transplant Side Effects for more on this). The new, grafted stem cells attack the body of the person who got the transplant. This is another reason its so important to find the closest match possible.
Many factors play a role in how the immune system knows the difference between self and non-self, but the most important for transplants is the human leukocyte antigen (HLA) system. Human leukocyte antigens are proteins found on the surface of most cells. They make up a persons tissue type, which is different from a persons blood type.
Each person has a number of pairs of HLA antigens. We inherit them from both of our parents and, in turn, pass them on to our children. Doctors try to match these antigens when finding a donor for a person getting a stem cell transplant.
How well the donors and recipients HLA tissue types match plays a large part in whether the transplant will work. A match is best when all 6 of the known major HLA antigens are the same a 6 out of 6 match. People with these matches have a lower chance of graft-versus-host disease, graft rejection, having a weak immune system, and getting serious infections. For bone marrow and peripheral blood stem cell transplants, sometimes a donor with a single mismatched antigen is used a 5 out of 6 match. For cord blood transplants a perfect HLA match doesnt seem to be as important, and even a sample with a couple of mismatched antigens may be OK.
Doctors keep learning more about better ways to match donors. Today, fewer tests may be needed for siblings, since their cells vary less than an unrelated donor. But to reduce the risks of mismatched types between unrelated donors, more than the basic 6 HLA antigens may be tested. For example, sometimes doctors to try and get a 10 out of 10 match. Certain transplant centers now require high-resolution matching, which looks more deeply into tissue types and allow more specific HLA matching.
There are thousands of different combinations of possible HLA tissue types. This can make it hard to find an exact match. HLA antigens are inherited from both parents. If possible, the search for a donor usually starts with the patients brothers and sisters (siblings), who have the same parents as the patient. The chance that any one sibling would be a perfect match (that is, that you both received the same set of HLA antigens from each of your parents) is 1 out of 4.
If a sibling is not a good match, the search could then move on to relatives who are less likely to be a good match parents, half siblings, and extended family, such as aunts, uncles, or cousins. (Spouses are no more likely to be good matches than other people who are not related.) If no relatives are found to be a close match, the transplant team will widen the search to the general public.
As unlikely as it seems, its possible to find a good match with a stranger. To help with this process, the team will use transplant registries, like those listed here. Registries serve as matchmakers between patients and volunteer donors. They can search for and access millions of possible donors and hundreds of thousands of cord blood units.
Be the Match (formerly the National Marrow Donor Program)Toll-free number: 1-800-MARROW-2 (1-800-627-7692)Website: http://www.bethematch.org
Blood & Marrow Transplant Information NetworkToll-free number: 1-888-597-7674Website: http://www.bmtinfonet.org
Depending on a persons tissue typing, several other international registries also are available. Sometimes the best matches are found in people with a similar racial or ethnic background. When compared to other ethnic groups, white people have a better chance of finding a perfect match for stem cell transplant among unrelated donors. This is because ethnic groups have differing HLA types, and in the past there was less diversity in donor registries, or fewer non-White donors. However, the chances of finding an unrelated donor match improve each year, as more volunteers become aware of registries and sign up for them.
Finding an unrelated donor can take months, though cord blood may be a little faster. A single match can require going through millions of records. Also, now that transplant centers are more often using high-resolution tests, matching is becoming more complex. Perfect 10 out of 10 matches at that level are much harder to find. But transplant teams are also getting better at figuring out what kinds of mismatches can be tolerated in which particular situations that is, which mismatched antigens are less likely to affect transplant success and survival.
Keep in mind that there are stages to this process there may be several matches that look promising but dont work out as hoped. The team and registry will keep looking for the best possible match for you. If your team finds an adult donor through a transplant registry, the registry will contact the donor to set up the final testing and donation. If your team finds matching cord blood, the registry will have the cord blood sent to your transplant center.
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Types of Stem Cell and Bone Marrow Transplants - American Cancer Society
Novel stem cell therapy for repair of knee cartilage – Mayo Clinic
Dec. 29, 2018
Mayo Clinic offers a unique regenerative medicine approach for repairing knee cartilage, which can be completed in a single surgery. The Food and Drug Administration approved the use of this technique, known as recycled cartilage auto/allo implantation (RECLAIM), in a trial utilizing the stem cell bank in the Mayo Clinic Center for Regenerative Biotherapeutics.
"Mayo is unique in having an adipose-derived allogeneic stem cell bank. It provides us with donor mesenchymal stem cells, which we mix with recycled autologous cells to quickly obtain enough cells to fill the patient's cartilage defect without operating twice," says Daniel B. Saris, M.D., Ph.D., an orthopedic surgeon at Mayo Clinic in Rochester, Minnesota, who specializes in knee surgery and focuses on regenerative medicine.
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RECLAIM mixes chondrons from debrided tissue with donor autologous stem cells to create a biologic filler for the repair of damaged knee cartilage. The procedure can be completed in a single surgery.
Dr. Saris previously performed the RECLAIM cartilage repair technique in Europe. "The results, about four years out, are very good comparable to or better than other cell therapies, except these patients achieve normal function after surgery about six months more quickly," he says.
Planning is underway for a clinical trial at Mayo Clinic. RECLAIM is used to repair symptomatic cartilage defects, usually resulting from trauma or an athletic injury. The procedure might be suitable for nonarthritic patients ages 18 to 50 who have fresh cartilage defects.
Existing cell therapy to repair knee cartilage generally involves surgically debriding the cartilage defect and then taking a biopsy of healthy cartilage from the patient. The biopsy is cultured in an outside laboratory, and the cultured cells are implanted weeks later. "We wanted to improve this technique because during the waiting period, the patient's life is on hold, costs increase and the logistics can be complex," Dr. Saris says.
RECLAIM's innovation starts with saving the patient's debrided tissue. "That tissue is always a bit frilly and is normally discarded," Dr. Saris says. "But we found that the cells in that tissue are still very viable. We recycle them."
The resected tissue is processed and, using a rapid isolation protocol, digested into chondrons. Mixing the chondrons with allogeneic stem cells from the stem cell bank provides sufficient cells to immediately re-inject into the patient.
"This is a highly innovative procedure," Dr. Saris says. "You have to find an intricate balance loading enough cells to grow into healthy tissue but not overloading the space so the cells are squished when the patient starts rehab."
Most patients return home on the day of surgery. They generally need to wait nine to 12 months before a full return to sports; that interval provides time for the cartilage to grow and the patient to regain muscle control. "But apart from sports, patients can go back to normal life within days and physical activities within three to four months of surgery," Dr. Saris says.
Mayo Clinic's multidisciplinary approach provides the range of care needed by patients at all stages of knee cartilage repair. Before surgery, advanced imaging helps pinpoint the cartilage defect. "Our physiotherapists and athletic trainers also determine prior to surgery how we can optimize the patient's musculoskeletal control and function, and then work with the patient on rehab after surgery," Dr. Saris says.
Mayo Clinic also has the breadth of orthopedic expertise to manage problems that patients often experience alongside damaged knee cartilage, such as varus deformity and anterior cruciate ligament or meniscus lesions. "If a cartilage repair procedure fails, it's generally because not enough attention was paid to other factors the meniscus or the knee's alignment or stability," Dr. Saris says. "Our unique multidisciplinary team looks at all aspects of a patient's care. Our chances of success for these complex biological reconstructions is therefore high."
The cartilage repair technique illustrates Mayo Clinic's commitment to applying regenerative medicine to orthopedic surgery. "We are focused on patient-centered progress," Dr. Saris says. "We want to make sure there is a safe and efficacious portfolio of regenerative medicine therapies for musculoskeletal problems."
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Novel stem cell therapy for repair of knee cartilage - Mayo Clinic
Islands for Sale in Florida, United States – Private Islands Online
ISLANDS FOR SALE IN United States
Florida has long been America's retirement mecca with its warm climate and proximity to the rest of the United States. Hurricanes are obviously a concern in this region, as is assuring your island stays high and dry. While private island prices in Florida may seem high to Americans, for Eu... + Read Moreropeans and others, the real estate feels like a bargain, particularly when figured in euros or pounds. Surrounded by water on three sides, Florida's coasts include the waters of the Gulf of Mexico, the Atlantic and the warm Caribbean bathes the Florida Keys. With an average of 300 days of full sunshine a year, it's easy to understand why Florida has such an active private island market.
Foreign Ownership Info for all States in the USAAmericas real estate laws create an open and reliable atmosphere for foreign investors. All private islands on the market in the U.S. can be bought freehold; there are no special requirements for foreign ownership. - Read Less
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Islands for Sale in Florida, United States - Private Islands Online