The Secret Behind Bill Gates’ Success Is Within Your Reach You must absolutely apply this secret to your life. An Interview That Has Become Legendary @ DECEMBER 18, 2019 – First images of an ‘upgraded’ CRISPR tool by Columbia University Irving Medical Center @ #CNN #News – Bill Gates predicted pandemic. Hear his advice now. YouTube Video @ Article: Age-Induced Reduction in Human Lipolysis: A Potential Role for Adipocyte Noradrenaline Degradation @ To slow the coronavirus death toll we may need to slow down ageing – The pandemic has overwhelmingly hit older people, leaving some longevity researchers wondering whether slowing ageing could be the key to beating the virus – By DAVID COX Friday 26 June 2020 @ https://en.wikipedia.org/wiki/Bill_Gates @ https://en.wikipedia.org/wiki/Computer

´´William Henry Gates III (born October 28, 1955) is an American business magnate, software developer, investor, and philanthropist. He is best known as the co-founder of Microsoft Corporation.[2][3] During his career at Microsoft, Gates held the positions of chairman, chief executive officer (CEO), president and chief software architect, while also being the largest individual shareholder until May 2014. He is one of the best-known entrepreneurs and pioneers of the microcomputer revolution of the 1970s and 1980s. Born and raised in Seattle, Washington, Gates co-founded Microsoft with childhood friend Paul Allen in 1975, in Albuquerque, New Mexico; it went on to become the world’s largest personal computer software company.[4][a]´´

https://en.wikipedia.org/wiki/Computer

´´The next great advance in computing power came with the advent of the integrated circuit (IC). The idea of the integrated circuit was first conceived by a radar scientist working for the Royal Radar Establishment of the Ministry of Defence, Geoffrey W.A. Dummer. Dummer presented the first public description of an integrated circuit at the Symposium on Progress in Quality Electronic Components in Washington, D.C. on 7 May 1952.[67] The first working ICs were invented by Jack Kilby at Texas Instruments and Robert Noyce at Fairchild Semiconductor.[68] ´´

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The Secret Behind Bill Gates’ Success Is Within Your Reach

You must absolutely apply this secret to your life.

Sylvain SaurelFollowDec 14 · 4 min read

Bill Gates is known to all for founding the Microsoft company that made computing with the Windows operating system available to the general public. Even better, Bill Gates has built on this success by investing his fortune wisely to consistently remain at the top of the world’s wealthiest people. At the end of 2019, his net worth is estimated at more than 106 billion dollars.


The Secret Of Bill Gates’ Success Is Intriguing

Bill Gates is the very example of a genius who has been able to make the most of exceptional capabilities to achieve immense success. As such, he is a role model for many people and all his speeches are eagerly awaited.

As is often the case with his friend Warren Buffett, people who have the opportunity to interact with Bill Gates invariably ask him the following question:

“What is the secret behind your success?”

Thus, many people think that there would be a unique secret behind the secret of a man like Bill Gates. Nothing is that simple in life, but a fundamental reason for its success may well exist. Also, would knowing this secret be enough for you to be able to reproduce it?

The answer depends solely on you and your will, in my opinion.


An Interview That Has Become Legendary

For several years now, I have often read a story about Bill Gates and an interview he might have given to a journalist one day. Actually, I do not know if this interview really took place or if it’s just some kind of urban legend that was launched one day and has grown over time.

Nevertheless, I find this story from Bill Gates’ interview very informative and I will tell you about it.

During this famous interview, a journalist asked Bill Gates:

“Mr. Gates, what is the secret of your success?”

Bill Gates did not answer this question directly and handed him a cheque telling her to write on it the amount of her choice.

The journalist was offended by this answer and replied to Bill Gates:

“Mr. Gates, I’m not talking about that.”

Then she repeated her question again:

“I ask you what is the secret of your success?”

Bill Gates did exactly the same thing and handed her that cheque again and told her to write the amount of her choice on it.

The journalist took the check and tore it up!

Bill Gates then told the journalist who was quite upset:

“The secret of my success is that I do not miss any opportunities like you just did. If you had that philosophy, you could have become the richest journalist in the world today.”


The Secret Behind Bill Gates’ Success Is To Seize Every Opportunity

The fall of this story clearly highlights the philosophy that enabled Bill Gates to achieve such success. Bill Gates seizes every golden opportunity that presents itself.

Bill Gates does not waste time by asking unnecessary questions as the journalist did during the interview.

This mindset allowed Bill Gates to develop Microsoft into the technology giant we know today. Of course, some will argue that it was in the right place at the right time when he founded Microsoft.

This is not totally false. But at that time, many other entrepreneurs were on the starting line with the same possibilities as him.

Bill Gates has made a difference through his strategic choices and long-term vision of the IT industry.

He then took immediate and massive actions to seize the opportunities that presented themselves. The result of this action-oriented philosophy has been spectacular as you know.


Conclusion

Many people envy the phenomenal success of Bill Gates who remains one of the richest men on the planet today. Rather than just looking at the result, you must go back to the roots of its success. As the anecdote of his interview with this journalist showed us, Bill Gates’ success is largely due to the fact that he has always been able to seize the opportunities that presented themselves.

So you can transpose the secret behind Bill Gates’ success into your life. To do this, you must seize the opportunities that present themselves to you by adopting an action-oriented mindset.

You will only be successful if you are able to take the immediate and massive actions required when golden opportunities arise.

So, if one day a billionaire gives you a blank check and asks you to write the amount of your choice on it, do not waste time with unnecessary questions and take action immediately.

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DECEMBER 18, 2019

First images of an ‘upgraded’ CRISPR tool

by Columbia University Irving Medical Center

First images of an 'upgraded' CRISPR tool
Structure of the INTEGRATE complex showing Cascade (dark blue), TniQ units (light blue), and guide RNA (red). Credit: Sternberg and Fernández Labs at Columbia University Irving Medical Center

Columbia scientists have captured the first images of a new gene editing tool that could improve upon existing CRISPR-based tools. The team developed the tool, called INTEGRATE, after discovering a unique “jumping gene” in Vibrio cholerae bacteria that could insert large genetic payloads in the genome without introducing DNA breaks.

In the new study, published today in Nature, the researchers harnessed a Nobel Prize-winning technique called cryo-electron microscopy to freeze the gene editing complex in action, revealing high-resolution details about how it works.

“We showed in our first study how to leverage INTEGRATE for targeted DNA insertions in bacterial cells,” says Sam Sternberg, Ph.D., assistant professor of biochemistry & molecular biophysics at Columbia University Vagelos College of Physicians and Surgeons, who led the research with Israel Fernandez, Ph.D., assistant professor of biochemistry & molecular biophysics at Columbia. “These new images, a wonderful collaboration with Israel Fernández’s lab, explain the biology with incredible molecular detail and will help us improve the system by guiding protein engineering efforts.”

Starts like CRISPR, but has a different ending

The researchers used a technique called cryo-electron microscopy, which involves flash freezing a sample of the gene editing complex in liquid nitrogen and bombarding it with electrons. They then used the images they captured with the electron microscope to generate atomic resolution models of the INTEGRATE system.

The structural model reveals that the complex is made up of two main sections that are arranged in a helical filament. The larger portion, called Cascade, winds around and carries a guide RNA that it uses to scan the cell for a matching sequence in DNA. Once it locates and binds the target sequence, it threads the DNA strand through the TniQ “transposition” proteins that sit on the end of the complex and recruit other enzymes that help modify the DNA.

The scanning mechanism of INTEGRATE appears to work in a similar way to other well-studied CRISPR systems, some of which also contain a Cascade complex with guide RNA. However, unlike other CRISPR systems that use Cascade to target DNA for cutting, the function of Cascade within INTEGRATE is to target DNA for highly accurate insertion of genetic payloads.

First images of an 'upgraded' CRISPR tool
Cryo-electron microscopy images of the INTEGRATE complex bound to DNA (arrows). Credit: Sternberg and Fernández Labs at Columbia University Irving Medical Center

“Visualizing biology on this scale is truly amazing and can easily excite even those unfamiliar with the topic. The quality of this work, and the speed at which it was accomplished, is emblematic of the collaborative environment afforded by great mentors like Sam and Israel,” says Tyler Halpin-Healy, a Ph.D. student in the cellular, molecular and biophysical studies graduate program at Columbia University Irving Medical Center and first author of the study.

In their previous study, Sternberg and colleagues used genetics and biochemistry to propose how the CRISPR machinery would functionally link to the transposition machinery—the molecules responsible for gene “jumping”—and the study proved their hypotheses were correct.

Why it matters

Many researchers around the world now use CRISPR-Cas9 to quickly and cheaply make precise modifications to the genome of a cell. However, most uses of CRISPR involve cutting both strands of the target DNA, and the DNA break must then be repaired by the host cell’s own machinery. Controlling this repair process is still a major challenge in the field, and undesired gene edits are often introduced inadvertently in the genome. Additionally, existing tools often perform poorly at inserting large genetic payloads in a precise fashion. Improving the accuracy of gene editing is a priority for researchers and is critical for ensuring the safety of therapies developed with this technique.

The new INTEGRATE system developed by the Sternberg lab can accurately insert large DNA sequences without relying on the cell’s machinery to repair the strands. As a result, INTEGRATE could prove to be a more accurate and efficient way of making certain gene modifications than the original CRISPR-Cas system that is widely in use. The new tool could also help scientists perform gene editing in cell types with limited DNA repair activity such as neurons, where attempts to use CRISPR have been comparatively less successful.

What’s next

In addition to informing future engineering efforts, the structures highlight a possible proofreading checkpoint. Existing CRISPR technologies often suffer from so-called “off-target effects,” in which unintended sequences are promiscuously modified. The new structures reveal how Cascade and TniQ work together to ensure that only the correct “on-target” sequences are marked for DNA insertion. The researchers plan to further explore this checkpoint while developing the tool for new therapeutic approaches to disease.

The paper, titled “Structural basis of DNA targeting by a transposon-encoded CRISPR-Cas system,” was published online Dec. 18 in the journal Nature.


Explore furtherNew gene editor harnesses jumping genes for precise DNA integration


More information: Structural basis of DNA targeting by a transposon-encoded CRISPR–Cas system, Nature (2019). DOI: 10.1038/s41586-019-1849-0 , https://nature.com/articles/s41586-019-1849-0Journal information:NatureProvided by Columbia University Irving Medical Center537 shares

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Age-Induced Reduction in Human Lipolysis: A Potential Role for Adipocyte Noradrenaline Degradation

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To slow the coronavirus death toll we may need to slow down ageing

The pandemic has overwhelmingly hit older people, leaving some longevity researchers wondering whether slowing ageing could be the key to beating the virus


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Marco Bertorello via Getty Images

In March, as Vadim Gladyshev shifted through the reams of data detailing the kinds of people who were more likely to fall victim to Covid-19, the Harvard biochemist started to wonder if we were thinking about the viral infection in the wrong way.

In Europe, 95 per cent of those killed by the disease were aged 60 or over. According to the UN, the fatality rate for those over 80 is five times the global average. Although many infectious diseases impact older people disproportionately, with Covid-19 the skew towards older people is devastating. Given all this, Gladyshev wondered, why aren’t we treating Covid-19 as a disease of ageing?

As he watched the global arms race to try and find a treatment which either neutralised the SARS-CoV-2 virus or dampen the overactive immune response which leads to many of the deaths, Gladyshev – one of the world’s leading experts on the causes of ageing – could not help but ponder if academics and pharmaceutical companies across the world were heading down the wrong path. “If Covid-19 has the greatest impact on the elderly, rather than targeting the virus, should we not be focusing more on strengthening the host?” he says.

Since the 1930s, scientists have sought clues on how to turn back the ageing process in humans by first trying to extend lifespan in rodents, with two drugs – rapamycin and metformin – showing signs of promise. While it is doubtful that these drugs would be useful in severe cases of Covid-19 where patients are already on ventilator support, Gladyshev’s idea was simple. Could prescribing these drugs to the elderly as preventative measures could give the most vulnerable a better chance of fighting off Covid-19, and prevent them getting to that stage?

Since April, his idea has been taken up by a series of scientists across the US ranging from pharmacologists at Thomas Jefferson University to the Boston-based biotech company resTORbio, who are now testing forms of rapamycin in a series of clinical trials over the coming months.

While rapamycin and metformin are typically known for their clinical uses in cancer and diabetes respectively, the reason why Gladyshev and other longevity scientists think that these drugs could protect the elderly from covid-19 is linked to theories regarding biological age. We typically measure age chronologically based on the number of years a person has been alive, but there is a school of thought that biological age – determined by biomarkers varying from DNA expression to the length of telomeres, the tips of chromosomes – can vary depending on factors ranging from lifestyle to genetics.

Nir Barzilai, founder of the Institute of Ageing Research at the Einstein College of Medicine in New York, argues that the reason some people are less prone to age-related diseases such as cardiovascular disease, dementia, cancer and infections, is because their biological age is much younger. “By the age of 65, half of people in Europe have two diseases or more, but half have less,” says Barzilai. “For me, this is due to their differing biological ages.”

Most of the evidence that drugs might be able to reverse some of the hallmarks of ageing, and thus make an elderly person more resilient to viral infections, comes from studies either in human cells or rodents. This data suggests that rapamycin has the potential to revitalise the body’s natural defence mechanisms within the lungs, stimulating cells such as macrophages – which are designed to seek out and remove viruses – to work more efficiently.

But there have also been further findings in humans which has given longevity researchers increased confidence that they are on the right lines. Back in March, doctors in Wuhan published a study showing that diabetics taking metformin were much less likely to die of Covid-19 than diabetics not on the drug, an interesting finding which backed up previous epidemiological data showing that it can improve lifespan in diabetics. An earlier clinical trial conducted by resTORbio, using a formulation of rapamycin called RTB101, reported that it could reduce rates of respiratory viral infections in healthy people over 65.

Nevertheless when the Covid-19 pandemic began, few specialists outside of longevity research were aware of the anti-ageing properties of these drugs. At the start of April, Edwin Lam – a pharmacology researcher at Thomas Jefferson University – was looking at a study from molecular biologists across the US which used computer models to predict which drugs performed best when it came to helping the body remove the virus. To his surprise, rapamycin and metformin ranked top, ahead of many highly touted alternatives such as hydroxychloroquine.

“Initially I thought this seemed far-fetched,” says Lam. “But then I looked further and found that some scientists had previously used a form of rapamycin called Sirolimus to treat people with severe cases of H1N1 bird flu. They saw a reduction in the viral load and better clinical outcomes. It had also shown antiviral activity in a preclinical model of Middle East Respiratory Syndrome. I presented this to my colleagues and we became really intrigued.”

Lam has now designed a placebo-controlled clinical trial to see whether rapamycin can reduce the viral load in 20 patients with mild to moderate cases of Covid-19. A similar study is also taking place at the University of Cincinnati. ResTORbio are now looking at whether giving 550 nursing home residents an oral capsule of RTB101 each day over a period of one month, could protect them from becoming severely infected with the virus, and needing hospitalisation.

“Nursing home residents have a very high risk of dying from Covid-19,” says Joan Mannick, co-founder and chief medical officer of resTORbio. “This elevated mortality has made the public acutely aware of the dysfunction of the aging immune system. I think the pandemic has the potential to catalyse interest in therapeutics that target aging biology as a new way to improve the function of aging organ systems.”

But other scientists looking at ways to protect the elderly from Covid-19 caution that while they will be monitoring the results of the trials with interest, the evidence regarding the effectiveness of anti-ageing drugs remains limited. “It’s an interesting approach, but the data will have to speak for itself,” says Ofer Levy, who heads the Precision Vaccines Program at Boston Children’s Hospital. “It’s all about safety and efficacy. Is it safe, how long can they be on it, and then is it effective? But it’s something to consider.”

Levy points to another potentially promising approach for protecting the elderly from Covid-19, vaccines which are specifically designed for older people. These typically contain additional chemicals known as adjuvants to try and kick-start the ageing immune system. It’s an approach which was successfully used by British pharma company GlaxoSmithKline to create the Shingrix vaccine in the past five years. This has shown to be highly effective in preventing shingles in people over 50, and Levy is looking to apply this strategy to a Covid-19 vaccine.

One of the ironies of vaccine development is that while over 65s stand to benefit most from immunisation, research has often shown that vaccines against influenza and other infections are at their least effective in the very old. This is thought to be due to changes in the blood which affect the immune response. “As we age, the blood plasma changes and we tend to develop a low level of inflammation in our bloodstream,” Levy says. “Because of this, when you try to immunise someone, you often get an incomplete response to the vaccine.

Instead, Levy’s group is designing a vaccine which is specifically modelled on older immune systems. “Our approach is to take blood donations from elderly volunteers, and then we isolate the immune cells in a dish,” he says. “We then screen lots of small molecules until we find ones which are like rocket fuel to the immune system, we add them to the vaccine and select the formulations which seem to work best against the coronavirus. This is completely different to normal vaccine development as we’re actually designing it with the ageing immune system in mind.”

He hopes that such a vaccine could be in clinical trials by autumn 2021. Barzilai points out that in the meantime there is some evidence to suggest that supplementary treatment with rapamycin could enhance the effectiveness of the first wave of vaccines when they become available, with Japanese company AnGes hoping to make their Covid-19 vaccine available at the start of next year. Rapamycin has previously been shown to enhance the effectiveness of the influenza vaccine. “I’m sure that the initial vaccines will not be effective in the elderly, because their designs ignore their immune deficiencies,” Barzilai says. “But rapamycin could make a difference.”

With the increased interest in rapamycin, longevity scientists predict that Covid-19 could prove to be a major boon for the field of anti-ageing research, a sector which has already been benefiting from injections of funding in recent years. Last year Barzilai received $75 million (£60.5m) to conduct the TAME clinical trial, looking at whether giving metformin to elderly people over a period of four to five years can give them more years of good health. Gladyshev says that the three Covid-19 clinical trials involving rapamycin could provide a whole host of information regarding its ability to reduce biological age.

However, Barzilai is still frustrated that many within the medical community appear to be unaware of the potential of these drugs. He points to the Wuhan study in March, saying that while similar findings have been observed in Italy and Spain, no one has conducted a clinical trial looking at whether administering metformin to the elderly population in general, can offer protective benefits against Covid-19.

“The major problem is that our health organisations are in silo and so ageing is often overlooked as a risk factor in these diseases,” he says. “For me, the question is why are we not using these two drugs on a wider scale to try and protect the vulnerable, when we already have information that they can offer benefit? Metformin has been used clinically for 60 years, it’s already known to be safe. If we just focus on stopping the disease in older people, the whole mortality issue would be different, the lockdowns wouldn’t need to happen, and the economic impacts would be less as well.”

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