2013 June 29 Saturday
Junk Sections Of Human DNA Not Really Junk After All

Most DNA in human chromosomes is not transcribed and translated into proteins. So the thinking in some circles has been that this DNA was just basically parasitic junk along for the ride. Since that view never made sense to me I'm happy to report that lots of the "junk" DNA regions get transcribed to make RNA molecules. Given the discoveries in recent years on small pieces of RNA as regulatory molecules it looks like large chunks of the genome code for complex regulatory mechanisms.

A new UC San Francisco study highlights the potential importance of the vast majority of human DNA that lies outside of genes within the cell.

The researchers found that about 85 percent of these stretches of DNA make RNA, a molecule that increasingly is being found to play important roles within cells. They also determined that this RNA-making DNA is more likely than other non-gene DNA regions to be associated with inherited disease risks.

This sort of RNA gets a number of names depending on the size and function and who is writing about it. Watch for non-protein-coding RNA (ncRNA) as a general term or microRNA (miRNA) for shorter signaling RNA pieces.

When will we find out the regulatory roles for most of the signaling RNA? I expect we will benefit from the development of delivery mechanisms to put miRNA into cells to alter gene expression and protein function.

Here is the research paper: The uncharted territory of DNA is transcribed into RNA. This transcribed RNA probably forms complex signaling networks.

Known protein coding gene exons compose less than 3% of the human genome. The remaining 97% is largely uncharted territory, with only a small fraction characterized. The recent observation of transcription in this intergenic territory has stimulated debate about the extent of intergenic transcription and whether these intergenic RNAs are functional. Here we directly observed with a large set of RNA-seq data covering a wide array of human tissue types that the majority of the genome is indeed transcribed, corroborating recent observations by the ENCODE project.

One implication of this research: Since more of the DNA is used more of the differences in DNA matter.

By Randall Parker 2013 June 29 01:52 PM 
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Healthy Menu Items Encourage Picking Of Unhealthy Items

When fast food restaurants add healthier items to their menus people respond by eating a larger amount of unhealthy food. Click thru and read the whole thing. The mind boggles.

“When you put a healthy option up there on an otherwise unhealthy menu, not only do we not pick it, but its presence on the menu leads us to swing over and pick something that’s worse for us than we normally would,” Mr. Fitzsimons said.

Take home: the first mistake is setting foot in a fast food restaurant. What might help: an online menu for ordering in advance. Imagine a menu which allowed you to set filters on what menu items you see. Then you could use a tablet or smart phone to order before you arrive. Just pick up your (healthy) food without having to order while in the store.

People can satisfy their need for healthy food just by looking at descriptions for it.

Why? Mr. Fitzsimons called the phenomenon “vicarious goal fulfillment.” By seeing a healthy menu option at a restaurant, “it basically satisfies that goal to be healthy,” he said, and gives consumers leeway to order what they want.

Human minds are not rational. We just flatter ourselves that we are much more sensible than the subconscious mind allows us to be.

We need the ability to reprogram our brain appetite circuitry to update it for an environment where calorie malnutrition is rare and obesity is commonplace.

By Randall Parker 2013 June 29 12:26 PM 
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Computer Model Insights On Skin Cell Aging

A computer model points to a depletion of stem cells as the biggest cause of skin aging.

The Sheffield/P&G team developed an "in silico" (computer) model of human skin biology, capturing how the outer layers of the skin are developed and maintained over time. This model simulation or "virtual" skin was then used to test the three most popular theories of how skin cells function to regenerate our skin, the largest human organ, over a three-year period. When the simulation was run according to two of the theories, the virtual skin failed to fully regenerate. Only one theory enabled the virtual skin to still be in good shape after three years, as Dr. Xinshan Li (University of Sheffield Faculty of Engineering) and Dr. Arun Upadhyay (P&G), the lead co-authors explained in their research.

What I want to know about stem cell therapies: How hard will they be to deliver once the stem cells exist?

Think about some day when we have the biotechnology to create safe youthful skin stem cells. How hard will it be to deliver them into the subdermal layer of the skin? The problem: stem cells are very small and need to be widely distributed across all the outer body right below the surface. Will we need, say, a needle robot that sticks us hundreds of thousands or millions of times and injects cells at each location? Imagine a needle robot that gradually moves over your skin sticking you repeatedly in a wave going up each arm and leg.

To put it another way: how far can we expect stem cells to travel in the subdermal layer? The farther they can travel the fewer places we need to insert them and the easier the insertion job. Can skin stem cells replicate and gradually move inches underneath the skin? Or only submillimeters? Does any reader have a good answer to this question or a reference to a discussion of the problem?

Every time skin stem cells gets activated to divide and produce some regular skin cells some of those stem cells are lost. They either entirely differentiate into non-stem cells or they die.

"The theory which seems to fit best says that skin has a population of 'sleeping' stem cells, which sit in the lowest layer of the skin but don't constantly divide to make new cells," Dr. Li said. "However, these sleeping cells can be called into action if the skin is damaged, or if the numbers of other types of more mature skin cells decrease, ensuring that the skin can be constantly regenerated under all conditions." The model showed that we gradually lose these sleeping stem cells over time-- which would explain why our ability to regenerate our skin reduces as we age. "Each time we wake up these cells, to heal a wound or replenish stocks of other cells, a few of them don't go back into sleep mode, so the population slowly reduces," says Dr. Li. "This explains why older skin is slower to heal and in part why our skin changes as we age. By understanding this mechanism better, it might be possible to find ways to combat the effects of aging on our skin."

Our stem cell reservoirs are depleting. Reverse that depletion and then a much longer, more youthful, and healthier life beckons.

Inactive stem cells with dangerous mutations are like sleeping time bombs waiting to go off.

"The stem cells can harbor mutations throughout the years, but with no effect if they're still in sleep mode," explains Dr. Li. "However, when they start to divide to heal a wound for example, this could trigger the cancer. If it's possible to study this phenomenon for long periods of time it may be possible to find ways to prevent the activation of mutated cells and therefore reduce the risk of developing the disease."

What would really help make stem cell therapies easier to do: the ability to direct stem cells to where they are most needed. These researchers directed the stem cells to bones. If similar techniques can be made work for most other tissue types then the delivery of stem cell therapies will become much easier.

SACRAMENTO — A research team led by UC Davis Health System scientists has developed a novel technique to enhance bone growth by using a molecule which, when injected into the bloodstream, directs the body's stem cells to travel to the surface of bones. Once these cells are guided to the bone surface by this molecule, the stem cells differentiate into bone-forming cells and synthesize proteins to enhance bone growth. The study, which was published online today in Nature Medicine, used a mouse model of osteoporosis to demonstrate a unique treatment approach that increases bone density and prevents bone loss associated with aging and estrogen deficiency.

We might have to go thru refurbishing periods where, say, for a week or month we get injections of stem cells tagged to go to different areas of the body.

By Randall Parker 2013 June 29 10:32 AM 
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2013 June 22 Saturday
Poor Water Quality Come The Zombie Apocalypse?

Max Brooks, author of The Zombie Survival Guide and World War Z, thinks come the zombie apocalypse most people will die from poor sanitation.

Believe him, most people in a zombie apocalypse would die not from zombie wounds or anything as sexy as that. They’d die, he explained, from the lack of a clean-water supply. And as anyone with even passing familiarity with his books “The Zombie Survival Guide” and “World War Z” knows, the biggest risk in a zombie invasion is fluid loss from all that running.

I have previously argued that a zombie apocalypse would be pretty easy to stop as long as we have enough bullets and other ways to do mass killing of zombies.That argument still seems right.

But suppose the zombies totally get out of hand. I could imagine this especially in lower lower gun ownership areas of Europe. Though the Swiss would likely do well. Okay, what to do? Basic survival 101. Get water filters, preferably portable water filters. Though if you live out in the country just roof solar panels and an electric pump would put you in good position. Ditto a hand water pump. Make sure you have a several hundred gallon storage tank in case the water table drops.

Come a zombie apocalypse islands seems preferable. It would be possible to keep the zombies off of islands or wipe them out with enough guns. Much harder to kill all the zombies on an overrun continent.

Someone with a sail boat, desalinating water filter, lots of weapons, and a few sniper friends could scope out an island and choose it for living. With people mostly dead the factory fishing ships would sail in far smaller number and so fishing could get pretty good.

Zombie Apocalypse scenarios have a lot of ovelap with many other survival scenarios. Civilization breaks down. Food supply and water supply are hard to come by. Predators suddenly loom large. But since zombies aren't too bright any organized groups of edgy people with strong loyalties and ruthlessness could certainly survive them and create safe zones.

By Randall Parker 2013 June 22 09:10 PM 
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2013 June 20 Thursday
Artificial Light Cutting Melatonin-Driven Sleep

We are staying up too late because our computer monitors, TVs, and room lights are boosting wakefulness by suppressing melatonin.

Before the widespread use of electric light, people probably experienced that second wind in the mid-afternoon, keeping them going until night fell. But light exposure after sunset signals 'daytime' to the SCN, shifting the clock later, postponing the second wind and delaying the onset of melatonin secretion.

LEDs are rich in short wavelength light in the frequency rate that suppresses melatonin production. Lack of sleep boosts appetite. I bet this is a substantial contributor to the rise in obesity.

We are in the midst of a little noticed large scale sleep deficiency.

Today, 30% of all employed US adults and 44% of night workers report averaging less than 6 hours sleep per night1, whereas 50 years ago less than 3% of the US adult population slept so little.

I am just about to try UV-blocking glasses in the evening to see if they'll get me sleepy sooner.

By Randall Parker 2013 June 20 08:46 PM 
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2013 June 17 Monday
Antidepressants Behind Obesity Epidemic?

Rats living stressed lives and taking fluoxetine (a.k.a Prozac or Sarafem) undergo long term increases in body weight.

SAN FRANCISCO—- Short-term use of antidepressants, combined with stress and a high-fat diet, is associated with long-term increases in body weight, a new animal study finds. The results were presented Sunday at The Endocrine Society's 95th Annual Meeting in San Francisco.

"Our study suggests that short-term exposure to stress and antidepressants, rather than a high-calorie, high-fat diet alone, leads to long-term body weight gain, accompanied with increased bone and spleen weights," said study lead author Suhyun Lee, a PhD candidate in the medical sciences at the John Curtin School of Medical Research at the Australian National University in Canberra, Australia.

What I would like to know: how much has too much evening blue light exposure from computers and house lights lowered melatonin production, reduced sleep, and therefore made people more prone to depression? Then antidepressants could just amount to a piling on where they increase obesity even more than lack of sleep does.

Anyone wear UV-blocking glasses in the evening to sleep better? I'm a pretty good sleeper. But blocking blue light in the evening might prevent slow creep toward later times to go to sleep and wake up.

By Randall Parker 2013 June 17 09:32 PM 
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2013 June 16 Sunday
More Telomerase Activity In Depressed People

Telomere caps on chromosomes shorten every time a cell divides and short telomeres interfere with cell division. However, in some conditions cellls turn on an enzyme, telomerase, that lengthens telomeres. Higher telomerase activity in depressed people might be an attempt by the body to boost neurogenesis against depression.

Now a research team led by Owen Wolkowitz, MD, professor of psychiatry at UC San Francisco, has found that within cells of the immune system, activity of an enzyme called telomerase is greater, on average, in untreated individuals with major depression. The preliminary findings from his latest, ongoing study was reported Wednesday at the annual meeting of the American Psychiatric Association in San Francisco.

Telomerase is an enzyme that lengthens protective end caps on the chromosomes’ DNA, called telomeres. Shortened telomeres have been associated with earlier death and with chronic diseases in population studies.

The heightened telomerase activity in untreated major depression might represent the body’s attempt to fight back against the progression of disease, in order to prevent biological damage in long-depressed individuals, Wolkowitz said.

Depression that comes on as some people get older might be a result of telomere shortening undermining the ability of the body to make replacement neurons.

The researchers made another discovery that may suggest a protective role for telomerase. Using magnetic resonance imaging (MRI), they found that, in untreated, depressed study participants, the size of the hippocampus, a brain structure that is critical for learning and memory, was associated with the amount of telomerase activity measured in the white blood cells. Such an association at a single point in time cannot be used to conclude that there is a cause-and-effect relationship with telomerase helping to protect the hippocampus, but it is plausible, Wolkowitz said.

Antidepressant drugs known to boost neurogenesis appear to boost telomerase activity.

Remarkably, the researchers also found that the enzyme’s activity went up when some patients began taking an antidepressant. In fact, depressed participants with lower telomerase activity at baseline — as well as those in whom enzyme activity increased the most with treatment — were the most likely to become less depressed with treatment.

Omega 3 fatty acids might slow the rate of telomere shortening.

Among this cohort of patients with coronary artery disease, there was an inverse relationship between baseline blood levels of marine omega-3 fatty acids and the rate of telomere shortening over 5 years.

By Randall Parker 2013 June 16 10:14 PM 
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2013 June 15 Saturday
Scientists Evolve A Virus So It Can Deliver Gene Therapy

Technology review headline: Virus That Evolved in the Lab Delivers Gene Therapy into the Retina. Works for mice. The scientists are now trying to make it work as well for monkeys.

From millions of random mutations, scientists identify a virus that could make gene therapy for inherited retinal diseases safer and more effective.

Viruses operate by injecting their DNA into a cell to program the cell to replicate their DNA. The ability to their shells to inject their DNA into cells make them obvious candidates to repurpose as delivery vehicles for gene therapy into cells. Viruses for gene therapy have been tried many times with limited success. The ability to turn the viruses thru guided evolution greatly improves the odds of eventual success.

While most gene therapy research is aimed to treating specific diseases once gene therapy becomes a sufficiently mature technology we can reuse it for rejuvenation. Find the genes that get the most damaged with age. Send in replacements and send in genes that will suppress the damaged copies.

Cell therapy is better when it can work because all accumulated damage can be removed. Gene therapy isn't going to enable us to fix every single accumulated DNA mutation that happens with aging. But gene therapy is great for cells that whould be hard to replace (e.g. nerves that store our memories or structural cells in key locations.

By Randall Parker 2013 June 15 12:18 PM 
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2013 June 13 Thursday
Consider How Long You Might Live After Retirement

You might live a long time even before considering the approaching biotech revolution. 10% of 65 year olds today will reach 95 years old. I think this is an overly conservative estimate. It is time to rethink career trajectories.

And with rising life expectancies, many people will have a lot of time: the average 65-year-old woman today can be expected to live to 86, a man to 84. One out of 10 people who are 65 today will live past 95, according to projections from the Social Security Administration.

For that 1 in 10 of 65 year olds who will live 30+ years that takes them to 2043. Imagine how radically the world will change by then. These figures do not yet reflect the impacts of coming rejuvenation therapies. Anyone who is going to live thru the next 30 years will witness the development of gene therapies, cell therapies, and tissue engineering that will enable the growth of replacement organs.

Already debt loads in retirees are rising. When they find themselves living longer their financial situations will become far worse. People need to account for this decades in advance.

It is easy to find news stories of people in their 50s and 60s unexpectedly finding themselves either unemployed or severely downshifted in their earnings power. Their skills have depreciated in value due to careers in declining ndustries, automation, and great changes in what skills are needed in many occupations. People laid off late in their careers take large pay cuts if they can find a new job. Yet rising life expectancies (with faster rises coming) bring the need to work longer and save more.

Consider the 45 year olds of today. In 2033 they'll hit 65. Surely their life expectancy at 65 will be much higher than a 65 year old of today. They'll enter old age with the next 20 years of biotechnological advances in treatments. Stem cell therapies will be common place by then. So the rate of aging should slow considerably and life expectancies will rise faster than the past trend.

What does this mean for career trajectories? You need to adjust your career path so that you will not decline in market value in your 50s and early 60s. Are you in your 40s or 50s and see that your industry or occupation faces worse times in the future? Does it seem plausible that automation will cut demand for people in your position? Lengthen your time horizon and invest in your career development. Your working years will probably last much longer than you expect. Aim to make career changes that can put you on a career arc that ensure you substantial market value well into your 70s.

By Randall Parker 2013 June 13 10:22 PM 
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2013 June 09 Sunday
Humans 100k Years From Now: Big Eyes And Big Heads?

Humans in 100,000 years? "Nickolay Lamm and Alan Kwan think future humans will sport bigger heads, bigger eyes and improved night vision."

100,000 years is the wrong time scale. As soon as we know what a substantial fraction of all the genetic variants do people will will doing embryo selection guided by genetic testing. I expect this to take off in under 10 years because genetic testing has become so cheap and genetic researchers have begun to find markers for IQ differences. Throw in markers for eye color, hair color, facial shape, dental attributes, skin tone, and other attributes and prospective parents who can afford IVF will mostly opt for it. This will accelerate human evolution by orders of magnitude.

Once it becomes possible to rewrite individual genetic letters I expect people will get variations of their own cells made that they'll use to create sperm and eggs to make genetically enhanced offspring. Then the rate of human evolution will accelerate by more orders of magnitude. So 100,000 years will not be necessary in order to see large changes in human features.

The biggest outward change: extreme beauty will become very common. 100 years from in advanced economies now only old people kept alive with rejuvenation therapies won't be extremely attractive. If the robots don't take over then the average young woman 100 years hence will be at least as good-looking as Giselle Bundchen.

By Randall Parker 2013 June 09 12:27 PM 
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2013 June 08 Saturday
Body Reshaping To Look Like Fictional Characters

How about plastic surgery to look like an elf, look like Superman, get star shapes on your forehead, become more tiger-like, or get pointy Spock Vulcan ears.. Recent advances in ear reshaping to get more pointed ears bodes well for elf lovers and Vulcan lovers.

Or how about eye implants to see into ultraviolet?

I see an angle here for a circus: bring out people who can much more realistically play assorted fictional characters.

By Randall Parker 2013 June 08 11:46 AM 
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Retirement, Money, And Rejuvenation Therapies

Low bond yields make retirement a dicey proposition.

Consider again the 65-year-old couple who are starting to draw down $1 million in savings this year: if they withdrew 3 percent, or $30,000, a year, rather than that standard rate of 4 percent, inflation-adjusted, there is still a one-in-three chance that they will outlive their money, under current market conditions.

Warning: this sort of projection is based on a business as usual (BAU) rate of progress in biomedical science. We are headed for a disruptive phase in development of biotechnology where we can begin to repair and replace aged tissue. Early stage rejuvenation therapies will arrive within the lifetimes of most people who are currently alive. But they will be expensive at first and not available as part of government-funded medical programs.

The nightmare: In some future decade you are 75 or 85 years old, your immune system is very weak, your joints are painful, and now one of your organs is failing. You have little money to live on. If you only had $250k you could get on an airplane and fly off to where you can get new one grown. In countries where a new medical treatment doesn't take 10 years to go thru regulatory processes replacement organs can be grown and lots of affluent people have them. But you are too poor to pay. Not a future I want.

Bottom line: If you want to guarantee your access to early stage rejuvenation therapies you need to save up and retain enough money to fund your own treatments. Prudent retirement planning should include planning for out-of-pocket payments for gene therapies, cell therapies, and growth of replacement organs.

By Randall Parker 2013 June 08 10:45 AM 
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2013 June 07 Friday
Electronic Tracking And Speedy Fugitive Capture

Susan Landau, author of Surveillance or Security?: The Risks Posed by New Wiretapping Technologies, told a New Yorker writer that electronic surveillance tools have slashed the time needed to capture fugitives.

. In fact, Landau told me, metadata and other new surveillance tools have helped cut the average amount of time it takes the U.S. Marshals to capture a fugitive from forty-two days to two.

Phone records are, btw, a form of metadata.

42 days to 2 days seems hard to believe. Though if fugitives rely on friends to stay free the ability to look back at, say, every phone call a person has made or received and to know instantly who those calls were to would make places to watch a lot easier to identify. Also, if a person has used affinity cards of grocery store chains and liquor store chains their past movements would be much easier to track. Ditto if a history of their cell phone cell tower uses could be reconstructed.

Anyone know what are the most important pieces of an electronic profile for tracking a fugitive? What do they do on the run? Ue their own cell phones? Do messaging on Facebook?

By Randall Parker 2013 June 07 07:55 PM 
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2013 June 04 Tuesday
GLYX-13 Lifts Depression As Well As Ketamine

Depression affects about 10% of the US adult population. How sad. But good news: The GLYX-13 causes anti-depression effects as fast and effectively as ketamine but without the major side effects of ketamine.

GLYX-13 and ketamine produced rapid acting (1 hour) and long-lasting (24 hour) antidepressant-like effects in the rats. Fluoxetine, an SSRI that typically takes from 2–4 weeks to show efficacy in humans, did not produce a rapid antidepressant effect in this study. As expected, the scrambled GLYX-13 showed no antidepressant-like effects at all. The researchers observed none of the aforementioned side effects of ketamine in the GLYX-13–treated rats.

This is great news for lab rats that work in oppressive, confined conditions. They can be happy and get more life satisfaction.

The drug is in phase 2 trials on humans.

Protein studies indicated an increase in the hippocampus of the NMDA receptor NR2B and a receptor for the chemical messenger glutamate called AMPA. Electrophysiology studies in this brain region showed that GLYX-13 and ketamine promoted long-lasting signal transmission in neurons, known as long-term potentiation/synaptic plasticity. This phenomenon is essential in learning and memory. The researchers propose how GLYX-13 works: GLYX-13 triggers NR2B receptor activation that leads to intracellular calcium influx and the expression of AMPA, which then is responsible for increased communication between neurons.

These results are consistent with data from a recent Phase 2 clinical trial, in which a single administration of GLYX-13 produced statistically significant reductions in depression scores in patients who had failed treatment with current antidepressants. The reductions were evident within 24 hours and persisted for an average of 7 days. After a single dose of GLYX-13, the drug’s antidepressant efficacy nearly doubled that seen with most conventional antidepressants after 4–6 weeks of dosing. GLYX-13 was well tolerated and it did not produce any of the schizophrenia-like effects associated with other NMDA receptor modulating agents.

The drug is the result of decades of research. The accumulated knowledge of neuroscience research is starting to pay off. It seems likely that in 10 years depression will be a very easily treated condition for most sufferers of depression.

By Randall Parker 2013 June 04 09:27 PM 
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2013 June 02 Sunday
General Anaesthesia Increases Dementia Risks

Prefer local anesthesia if you ever have a choice.

Exposure to general anaesthesia increases the risk of dementia in the elderly by 35%, says new research presented at Euroanaesthesia, the annual congress of the European Society of Anaesthesiology (ESA). The research is by Dr Francois Sztark, INSERM and University of Bordeaux, France, and colleagues.

Postoperative cognitive dysfunction, or POCD, could be associated with dementia several years later. POCD is a common complication in elderly patients after major surgery. It has been proposed that there is an association between POCD and the development of dementia due to a common pathological mechanism through the amyloid β peptide. Several experimental studies suggest that some anaesthetics could promote inflammation of neural tissues leading to POCD and/or Alzheimer's disease (AD) precursors including β-amyloid plaques and neurofibrillary tangles. But it remains uncertain whether POCD can be a precursor of dementia.

We either need better anaesthesia drugs or other drugs that cancel out their inflammatory effects. If I was going to have to get put under for surgery I would eat an anti-inflammatory diet. Most notably, I'd eat salmon every day for the omega 3 fatty acids and I'd eat even more fruits and vegetables than I normally do. Less red meat and refined grains, more fish,fruits, vegetables.

What we will most need anaesthesia drugs for: surgery to replace old organs with new organs grown in organ vats from our own (rejuvenated) cells.

By Randall Parker 2013 June 02 09:34 AM 
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2013 June 01 Saturday
Where Are The Alien Megastructures?

Check out The Hunt for Alien Megastructures by Markus Hammond. Some researchers are looking for signs of Dyson spheres.

To find a Dyson sphere, you need to look for a specific signature of infrared light, emitted at just the right set of wavelengths.

And that’s just what an ongoing project, headed by Dick Carrigan at Fermilab, has been doing.

Will alien species think building Dyson spheres brings the risk of unwanted hostile attentions? My guess is some will think that way. The ones that do not think that way might eventually get wiped out. Though their Dyson spheres would survive perhaps for thousands of years before another race's attack fleet could reach it.

Does the vastness of the expanses between stars make interstellar travel so hard that interstellar attacks are rarely attempted? Or do aggressors send nanobots to carry out their attacks? Also, are Dyson sphere builders likely to be able to repel a nanobot attack?

By Randall Parker 2013 June 01 04:31 PM 
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