Researchers Solve Anti-aging Mystery – Identify Gene Responsible for Cellular Aging

TOPICS:AgingCell BiologyGenetics

By ALPHAMED PRESS NOVEMBER 30, 2020

Cellular reprogramming can reverse the aging that leads to a decline in the activities and functions of mesenchymal stem/stromal cells (MSCs). This is something that scientists have known for a while. But what they had not figured out is which molecular mechanisms are responsible for this reversal. A study released today in STEM CELLS appears to have solved this mystery. It not only enhances the knowledge of MSC aging and associated diseases, but also provides insight into developing pharmacological strategies to reduce or reverse the aging process.

The research team, made up of scientists at the University of Wisconsin-Madison, relied on cellular reprogramming — a commonly used approach to reverse cell aging — to establish a genetically identical young and old cell model for this study. “While agreeing with previous findings in MSC rejuvenation by cellular reprogramming, our study goes further to provide insight into how reprogrammed MSCs are regulated molecularly to ameliorate the cellular hallmarks of aging,” explained lead investigator, Wan-Ju Li, Ph.D., a faculty member in the Department of Orthopedics and Rehabilitation and the Department of Biomedical Engineering.

When mesenchymal stem/stromal cells (MSCs) age, the transcription factor GATA6 is increasingly produced in the cell to induce aging response. By transcription factor-based cellular reprogramming, aged MSCs are rejuvenated with a reduction in GATA6 effects on cellular aging. Credit: AlphaMed Press

The researchers began by deriving MSCs from human synovial fluid (SF-MSCs) — that is, the fluid found in the knee, elbow and other joints — and reprogramming them into induced pluripotent stem cells (iPSCs). Then they reverted these iPSCs back to MSCs, in effect rejuvenating the MSCs. “When we compared the reprogrammed MSCs to the non-rejuvenated parental MSCs, we found that aging-related activities were greatly reduced in reprogrammed MSCs compared to those in their parental lines. This indicates a reversal of cell aging,” Dr. Li said.

The team next conducted an analysis of the cells to determine if there were any changes in global gene expression resulting from the reprogramming. They found that the expression of GATA6, a protein that plays an important role in gut, lung and heart development, was repressed in the reprogrammed cells compared to the control cells. This repression led to an increase in the activity of a protein essential to embryonic development called sonic hedgehog (SHH) as well as the expression level of yet another protein, FOXP1, necessary for proper development of the brain, heart and lung. “Thus, we identified the GATA6/SHH/FOXP1 pathway as a key mechanism that regulates MSC aging and rejuvenation,” Dr. Li said.

“Identification of the GATA6/SHH/FOXP1 pathway in controlling the aging of MSCs is a very important accomplishment.” Said Dr. Jan Nolta, Editor-in-Chief of STEM CELLS. “Premature aging can thwart the ability to expand these promising cells while maintaining function for clinical use, and enhanced knowledge about the pathways that control differentiation and senescence is highly valuable.”

To determine which of the Yamanaka transcription factors (four reprogramming genes used to derive iPSCs) were involved in repressing GATA6 in the iPSCs, the team analyzed GATA6 expression in response to the knockdown of each factor. This yielded the information that only OCT4 and KLF4 are able to regulate GATA6 activity, a finding consistent with that of several previous studies.

“Overall, we were able to demonstrate that SF-MSCs undergo substantial changes in properties and functions as a result of cellular reprogramming. These changes in iPSC-MSCs collectively indicate amelioration of cell aging. Most significantly, we were able to identify the GATA6/SHH/FOXP1 signaling pathway as an underlying mechanism that controls cell aging-related activities,” Dr. Li said.

“We believe our findings will help improve the understanding of MSC aging and its significance in regenerative medicine,” he concluded.

Reference: “GATA6 regulates aging of human mesenchymal stem/stromal cells” by Hongli Jiao, Brian E. Walczak, Ming‐Song Lee, Madeleine E. Lemieux and Wan‐Ju Li, 30 November 2020, STEM CELLS.
DOI: 10.1002/stem.3297

Like a Leaf – New Artificial Photosynthesis Method to Capture CO2 Directly From the Air and Turn It Into Fuel

TOPICS:Argonne National LaboratoryCarbon CaptureDOEEnergy

By ARGONNE NATIONAL LABORATORY, NOVEMBER 29, 2020

Argonne and SLAC will develop artificial photosynthesis methods to enable direct air capture of CO₂ while expanding sources of energy through the conversion of CO₂ to fuels and other useful chemicals.

In this project, researchers will explore a molecular photoreactor that captures CO2 and converts it to fuels and useful chemicals. (Image by Argonne National Laboratory.

Leaves make it look easy, but capturing and using carbon dioxide (CO₂) from the air is a challenging process for scientists to mimic.

To artificially capture CO₂, chemists have developed ways to “scrub” it from air using chemicals that react very favorably with it. But even after it is captured, it’s often difficult to release and use for artificial photosynthesis.

The U.S. Department of Energy’s (DOE) Argonne National Laboratory and SLAC National Accelerator Laboratory will receive $4.5 million over three years from the DOE for research aimed at capturing carbon dioxide directly from air and converting it to useful products by artificial photosynthesis.

“We were thrilled to get the opportunity to do new science and to work on this challenge. It would be enormously satisfying to open up a new, environmentally sound means of generating energy. A major advancement in this area would be the highlight of my career.” — Ksenija Glusac, Argonne chemist, Solar Energy Conversion group, Chemical Sciences and Engineering division

CO₂ capture involves trapping the gas, transporting it to a storage location and isolating it. Together, Argonne and SLAC will focus on developing photochemical methods that enable CO₂ capture directly from air and that combine this capture with photochemical conversion to fuels and value-added chemicals.

Their goal is to improve the environment and expand sources of energy through the conversion of CO₂ to fuels and other value-added chemicals such as methanol and acrylic acid derivatives — both of which are used by the chemical industry to make polymers, including resins, plastics and glues. Methanol also can be used as a fuel to generate electricity.

Ksenija Glusac, a chemist with the Solar Energy Conversion group in the Chemical Sciences and Engineering division at Argonne, will lead Argonne’s efforts as the principal investigator for the group.

Glusac has worked in the field of artificial photosynthesis since 2000, but combining CO₂ capture with photosynthesis is a new direction for her and her team.

“We were thrilled to get the opportunity to do new science and to work on this challenge,” said Glusac, who is also an associate professor of chemistry at the University of Illinois at Chicago. “It would be enormously satisfying to open up a new, environmentally sound means of generating energy.”

This photoreactor will be built up of molecular lego pieces, each designed to perform a certain function: chromophores that absorb and harvest the sunlight, molecules that capture CO2 from the atmosphere and catalysts that convert CO2 to value-added chemicals. Credit: Argonne National Laboratory

Glusac’s team has already contributed significantly to the field of artificial photosynthesis. After years of studying the interaction between matter and electromagnetic radiation, they expanded scientists’ understanding of what happens in materials in regard to the absorption of light — and the conversion of that light to energy.

“The current project builds on our extensive experience and opens up the opportunity of combining CO₂ capture with photosynthesis,” Glusac said.

Glusac and her team plan to use Argonne’s Advanced Photon Source (APS), SLAC’s Stanford Synchrotron Radiation Lightsource (SSRL) and SLAC’s Linac Coherent Light Source (LCLS) — all are DOE Office of Science User Facilities — to collect X-ray absorption and scattering measurements to better understand the CO₂ capture and photo-conversion mechanisms.

The APS’s high-energy storage ring generates ultrabright, hard X-ray beams for research in almost all scientific disciplines while SSRL provides electromagnetic radiation in the X-ray, ultraviolet, visible and infrared realms produced by electrons circulating in a storage ring. LCLS takes X-ray snapshots of atoms and molecules at work, providing atomic resolution detail on ultrafast timescales to reveal fundamental processes in materials, technology and living things.

Glusac and her team will take these measurements from samples of supramolecular structures called MOFs (metal-organic frameworks) that can absorb and harvest solar light and nodes that host two types of catalysts: reduction catalysts that can capture CO₂ from the air and reduce it to value-added chemicals and oxidation catalysts that can convert water to oxygen.

“Our approach aims to combine CO₂ capture and artificial photosynthesis into a single process, called photoreactive capture,” Glusac said. “We will explore molecular photoreactors that can both scrub CO₂ and use sunlight to convert it into useful chemicals. We have great hope for this endeavor.”

Argonne’s Laboratory Computing Resource Center will be used to perform the computational investigations of CO₂ capture and conversion mechanisms.

In addition to Glusac, Argonne’s team includes Lin Chen, David Kaphan, Karen Mulfort, Alex Martinson, David Tiede and Peter Zapol. Amy Cordones-Hahn from SLAC rounds out the group.

Projects were selected by competitive peer review and supported by DOE’s Office of Science.

Researchers find how stress and the circadian clock affect sleep

by Nagoya University

A Nagoya University-led research team in Japan has found a new neural pathway that links the circadian clock, stress, and wakefulness in mammals. The team identified a neuron, called the corticotropin-releasing factor (CRF) neuron, that becomes excessively active when the mammal is under stress, which could trigger insomnia and other sleep disorders. Their findings were recently published in the journal Science Advances.

Living organisms exhibit a 24-hour oscillation called the circadian rhythm. In mammals, the central circadian clock, located in the brain’s suprachiasmatic nucleus (SCN) neurons, regulates the sleep-wake cycle. However, in the event of life-threatening situations, the circadian rhythm signal is shut off to keep the animal awake so that it can escape from danger even when it would normally be time to sleep. Although the temporary shutoff of the sleep-wake cycle is necessary for survival, excessive or prolonged stress caused by such dangers can trigger insomnia and other sleep disorders.

“It is well-known that the circadian clock and stress have an effect on sleep, but it was unclear which neural pathway is crucial for the circadian regulation of sleep and wakefulness,” says Dr. Daisuke Ono of the Research Institute of Environmental Medicine at Nagoya University. To determine the pathway, a Nagoya University research team led by Prof. Akihiro Yamanaka and Dr. Ono, in collaboration with Takashi Sugiyama at Olympus Corporation in Japan, conducted a study using mice.

The researchers focused on CRF neurons—which are known to play a role in stress response—that are located in the paraventricular nucleus of the hypothalamus. They investigated how sleep and wakefulness in mice would be affected when the CRF neurons were activated. The results showed that the activated CRF neurons kept the animals awake and made them move around vigorously, indicating that their wakefulness was promoted. The researchers also observed that CRF neurons remained active when the mice were awake, and that when the neurons’ activity was suppressed, the animals’ wakefulness and locomotor activities were reduced.

Further investigations also showed that inhibitory neurons in the SCN, called GABAergic neurons, play a significant role in regulating the activity of CRF neurons, and that the activation of CRF neurons stimulates orexin neurons in the lateral hypothalamus, which results in the promotion of wakefulness.

The team thus concluded that GABAergic neurons in the SCN control the activity of CRF neurons, which ultimately regulates the sleep-wake cycle. “We identified this neural pathway in mice, which are nocturnal animals. Further studies are required to elucidate how the nocturnal and diurnal difference is regulated in the brain,” says Dr. Ono.

“In today’s society, sleep disorders are a serious problem. We hope our finding will contribute to the development of new therapies for insomnia and other sleep disorders caused by stress or a disturbed circadian rhythm.”

The paper, “The mammalian circadian pacemaker regulates wakefulness via CRF neurons in the paraventricular nucleus of the hypothalamus,” was published in the journal Science Advances on November 6, 2020.

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Explore furtherScientists identify brain cells that drive wakefulness and resist general anesthetics

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More information: Daisuke Ono et al. The mammalian circadian pacemaker regulates wakefulness via CRF neurons in the paraventricular nucleus of the hypothalamus, Science Advances (2020). DOI: 10.1126/sciadv.abd0384Journal information:Science AdvancesProvided by Nagoya University

Gut microbes: The key to normal sleep

by University of Tsukuba

With fall and winter holidays coming up, many will be pondering the relationship between food and sleep. Researchers led by Professor Masashi Yanagisawa at the University of Tsukuba in Japan hope they can focus people on the important middlemen in the equation: bacterial microbes in the gut. Their detailed study in mice revealed the extent to which bacteria can change the environment and contents of the intestines, which ultimately impacts behaviors like sleep.

The experiment itself was fairly simple. The researchers gave a group of mice a powerful cocktail of antibiotics for four weeks, which depleted them of intestinal microorganisms. Then, they compared intestinal contents between these mice and control mice who had the same diet. Digestion breaks food down into bits and pieces called metabolites. The research team found significant differences between metabolites in the microbiota-depleted mice and the control mice. As Professor Yanagisawa explains, “we found more than 200 metabolite differences between mouse groups. About 60 normal metabolites were missing in the microbiota-depleted mice, and the others differed in the amount, some more and some less than in the control mice.”

The team next set out to determine what these metabolites normally do. Using metabolome set enrichment analysis, they found that the biological pathways most affected by the antibiotic treatment were those involved in making neurotransmitters, the molecules that cells in the brain use to communicate with each other. For example, the tryptophan–serotonin pathway was almost totally shut down; the microbiota-depleted mice had more tryptophan than controls, but almost zero serotonin. This shows that without important gut microbes, the mice could not make any serotonin from the tryptophan they were eating. The team also found that the mice were deficient in vitamin B6 metabolites, which accelerate production of the neurotransmitters serotonin and dopamine.

The team also analyzed how the mice slept by looking at brain activity in EEGs. They found that compared with the control mice, the microbiota-depleted mice had more REM and non-REM sleep at night—when mice are supposed to be active—and less non-REM sleep during the day—when mice should be mostly sleeping. The number of REM sleep episodes was higher both during the day and at night, whereas the number of non-REM episodes was higher during the day. In other words, the microbiota-depleted mice switched between sleep/wake stages more frequently than the controls.

Professor Yanagisawa speculates that the lack of serotonin was responsible for the sleep abnormalities; however, the exact mechanism still needs to be worked out. “We found that microbe depletion eliminated serotonin in the gut, and we know that serotonin levels in the brain can affect sleep/wake cycles,” he says. “Thus, changing which microbes are in the gut by altering diet has the potential to help those who have trouble sleeping.”

So, this holiday season, when you’re feeling sleepy after eating tryptophan-stuffed turkey, please don’t forget to thank your gut microbes!

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Explore furtherGuts and brains: How microbes in a mother’s intestines affect fetal neurodevelopment

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More information: Yukino Ogawa et al. Gut microbiota depletion by chronic antibiotic treatment alters the sleep/wake architecture and sleep EEG power spectra in mice, Scientific Reports (2020). DOI: 10.1038/s41598-020-76562-9Journal information:Scientific ReportsProvided by University of Tsukuba

BBC Launches Artificial Intelligence Tool To Read Its Articles To Listeners

November 26, 20205:03 AM ETHeard on Morning Edition

SHANNON BONDTwitterLISTEN·3:403-Minute ListenAdd toPLAYLIST

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The BBC is launching a new audio tool that uses artificial intelligence to read articles from its website aloud with a voice that speaks in a friendly, easy to understand northern British accent.

DAVID GREENE, HOST:

The BBC is one of the world’s most recognized broadcasters. Maybe you’ve heard this before.

(SOUNDBITE OF BBC BROADCAST)

UNIDENTIFIED BROADCASTER #1: Hello. And welcome to Newshour from the BBC World Service, coming to you live from our studios in central London.

GREENE: But when the BBC wanted to step up its audio game online, it wanted a more informal, friendlier voice than that. So it turned to artificial intelligence. NPR tech correspondent Shannon Bond introduces us to their newest sound.

COMPUTER-GENERATED VOICE: I’m the BBC’s synthetic voice, and I can read out articles from bbc.com.

SHANNON BOND, BYLINE: This is the first time I’m meeting this voice, which I’m sorry to say doesn’t have a name. The BBC told me I could ask it anything, so I asked it to explain how it works.

COMPUTER-GENERATED VOICE: It’s easy. I take the text that’s on the screen and read it out loud. Well, OK, maybe it’s not quite that simple. There’s a lot of tech going on in the background.

BOND: The BBC developed the voice with engineers at Microsoft using machine learning.

COMPUTER-GENERATED VOICE: They based it on many hours of human recordings and finely tuned it to create the voice you hear now. Pretty clever, eh?

BOND: A lot of publishers are trying these experiments to turn text into speech to make their websites and apps accessible for people who have a hard time seeing and to keep people engaged even if they’re too busy to sit down and read. So the BBC did a lot of research and decided to shed one of its best-known traits, the very proper accent known as the Queen’s English.

(SOUNDBITE OF BBC BROADCAST)

UNIDENTIFIED BROADCASTER #2: Here is the Air Ministry’s weather forecast for tomorrow.

BOND: Online, the BBC wanted a voice that’s more easygoing, one you could imagine having a pint with.

COMPUTER-GENERATED VOICE: I’m British, so I say tomahto (ph) while you say tomayto (ph). I’m also Northern, aka not from London, so I say Bath, while the Queen of England might say Bahth (ph).

BOND: Bath, Bahth. OK, that might not sound like a big deal to American ears, but on the other side of the pond, it really matters.

COMPUTER-GENERATED VOICE: In the U.K., Northerners are known for sounding friendly. I hope I do, too.

BOND: That tone also sets the BBC apart from the audio technology other news organizations are using.

CLAIRE: This is your Washington Post Election 2020 results update. I’m Claire, elections AI presenter for the Post.

BOND: Claire is all business, no drama. At the other end of the spectrum, there’s The New York Times.

UNIDENTIFIED VOICE ACTOR: Black theater is having a moment. Thank Tyler Perry – seriously.

BOND: The Times bought a company this year called Audm, which produces audio stories with professional voice actors. The BBC is aiming for somewhere in the middle. Here’s what its voice sounds like reading a recent story.

COMPUTER-GENERATED VOICE: But when the office temporarily closed eight months ago due to the pandemic, Domino wasn’t wistful about losing his daily dose of corporate culture, the view or free kombucha.

BOND: So now when you might think about flipping on the radio or a podcast, the BBC hopes you’ll try out a news story or feature.

COMPUTER-GENERATED VOICE: Life can get busy, so I can help by reading articles out loud, letting you get on with other things at the same time. You might need to go for a run, pick the kids up from school or make supper, which I believe Americans call dinner.

BOND: But do people really want to listen to a robotic voice, even a friendly one? I asked Nick Quah, who writes the audio industry newsletter Hot Pod. He says that depends on whether the AI can fool you into thinking it’s a real person.

NICK QUAH: Could you – (laughter) can it be an automated delivery of information that doesn’t feel mechanical, that feels vaguely believable as (laughter) a source of like, you know, that intimacy that people look for in the audio format?

BOND: And when it comes to that question, we humans still have an edge over the robots. Just ask Siri.

SIRI: Shannon Bond, NPR News.

Copyright © 2020 NPR. All rights reserved. Visit our website terms of use and permissions pages at www.npr.org for further information.

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10 Tips to Fall Back Asleep After Waking Up at Night

• Tips
• After a nightmare
• When you’re stressed
• Prevention
• Seeking medical help
• Summary

The inability to fall back asleep after waking up is medically known as sleep-maintenance insomnia. Studies have found that anywhere from 10 to 60 percentTrusted Source of people experience insomnia.

Other forms of insomnia can cause:

• difficulty falling asleep
• frequent awakenings
• spontaneous early morning awakenings

If you’re dealing with sleep-maintenance insomnia, it’s a good idea to look for potential reasons why you may be waking up in the first place. Needing to use the bathroom, a beam of early morning sunlight shining through your window, or loud sounds are a few of the potential causes.

Sometimes, waking up in the middle of the night is unavoidable. Having a strategy in place to help you get back to sleep can help you minimize the amount of time you spend staring at the ceiling.

Let’s go over 10 tips to fall back asleep after waking up at night. We’ll also look at what you can do if your insomnia is caused by stress or nightmares.

How to go back to sleep after waking up in the middle of the night

If you’re having trouble getting back to sleep after waking up, it’s a good idea to avoid anything mentally stimulating and to focus on relaxing. The following 10 tips may help you.

1. Get rid of bright lights or loud sounds

If you’re having trouble falling back asleep, look for any lights in your bedroom that may be disturbing you. LED lights from electronics and light coming through your window may it more difficult to fall back asleep.

If a disturbing sound is coming through your window from outside, try shutting your window to block it out. Using earplugs, turning on a fan, or listening to white noise can also help you drown out disturbing sounds.

2. Get out of bed and move

Many sleep experts recommend getting out of bed and going to a different room if you’re unable to fall back asleep within about 20 minutes.

Moving into a different room and doing something relaxing to distract your mind for a few minutes may make it easier to fall back asleep when you return.

3. Avoid staring at the clock

Staring at the clock may make you feel anxious about not sleeping, especially if you already deal with generalized anxiety disorder.

Research from 2019Trusted Source found that the link between anxiety and sleep may work both ways. People who deal with anxiety often worry about falling asleep and people who have trouble falling asleep often feel anxious.

4. Avoid checking your phone or other screens

Screens from smartphones and other electronics emit blue light that may suppress your body’s melatonin production. Melatonin is a hormone made by the pineal gland in your brain that helps regulate your circadian rhythm and sleep cycles.

While it’s best to avoid checking your phone at night because of the potential for mental stimulation, there are some ways to reduce your exposure to blue light.

Many devices offer a nightshift mode that changes your screen to a warmer tone. Glasses with amber lenses are also an inexpensive way to block out blue light.

5. Meditate or try breathing exercises

Performing breathing exercises or meditating may help calm your mind and induce sleep. These techniques may also distract you from worrying about falling asleep.

One exercise you can use is called the 4-7-8 breathing technique. With this technique, you inhale through your nose for 4 seconds, hold your breath for 7 seconds, and exhale through your mouth.

6. Relax your muscles

One technique that many people find helps them relax and sleep is performing a full-body body scan.

Here’s one way you can perform a body scan:

1. Close your eyes and breathe slowly.
2. Focus on your face and think about relaxing each of the muscles.
3. Move to your neck and shoulders and think about relaxing them too.
4. Continue relaxing muscles in different parts of your body until you make it to your feet.

7. Keep your lights off

Even if you get out of bed, resist the temptation to turn on your lights. As with phone screens, the bright light can interfere with your body’s production of melatonin and stimulate wakefulness.

8. Focus on something boring

Any variation of the classic “counting sheep” technique, or a boring task that occupies your mind, may help distract you and make falling asleep easier. Reading a boring article or book may also work.

A part of your brain called the nucleus accumbens plays a role in motivation and pleasure. Research from 2017Trusted Source suggests that this part of your brain might be the reason why you often feel sleepy when bored.

9. Listen to relaxing music

Relaxing music may help relax your mind and coax you to sleep. It can also block sounds that may be disrupting your sleep.

Research from 2018Trusted Source has found that personal preference plays a large role in determining what type of music is best at stimulating sleep for each individual. You may want to experiment with several different types until you find one that works for you.

10. Try sleep apps

Many people find that sleep apps help them fall asleep faster by making them feel relaxed. There are many sleep apps on the market that offer relaxing stories, music, or sounds. Many of these apps offer free trials to give you time to find one that works for you.

How to go back to sleep after a nightmare

If you wake up in the middle of the night from a nightmare and have trouble getting back to sleep, you can use many of the same techniques mentioned above to clear your mind and relax:

• Use the 4-7-8 breathing technique or other mediation technique to slow your heart rate and breathing.
• Leave the room or try sleeping somewhere else.
• Listen to music that makes you feel calm.
• Focus your attention on something else for a few minutes.
• Turn on a fan or air conditioner if you feel hot.

How to go back to sleep when stressed

Stress and anxiety can make falling asleep difficult. Many people find that journaling about the things that stress them out helps relax and clear their minds.

You can also use some other techniques mentioned above, such as:

• mediation and breathing techniques
• focusing on something boring
• getting up and moving to a different room
• performing a body scan
• meditating

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What to do if you’re waking up too early

If you’re waking up early in the morning, ask yourself if there’s an obvious cause. Do you wake up needing to use the bathroom? Are you particularly stressed right now?

If the cause isn’t obvious, you can try improving your overall sleep habits to improve your sleep quality. Here are some tips:

• Avoid liquids right before bed.
• Exercise regularly during the day.
• Keep screens out of your bedroom.
• Avoid screens 2 hours before bed, or use night mode.
• Avoid caffeine past mid-afternoon.
• Avoid nicotine and alcohol.
• Cover or turn off lights in your room.
• Avoid naps during the day, especially late in the day.
• Try to adopt a consistent sleep schedule.

When to see a doctor if you keep waking up at night

The occasional night of disrupted sleep isn’t a cause for concern, but if it’s becoming a pattern, you may want to talk with a doctor. They may be able to help you identify the cause of your poor sleep and help you find ways to adjust your sleep habits.

A doctor may recommend that you see a sleep specialist to look for an underlying cause or sleep disorder. A psychologist or psychiatrist may be able to help you deal with psychological issues disrupting your sleep, and a neurologist can help identify a physiological cause.

Takeaway

Waking up in the middle of the night and not being able to fall back asleep is called sleep-maintenance insomnia. Many people find that focusing on something relaxing or that lets them clear their mind helps them fall asleep faster.

If you can’t sleep after 20 minutes, you may want to move to another room for a few minutes before returning to bed.

But if you notice that your insomnia is becoming a pattern, you may want to talk with a doctor. They may be able to help you find the root of your insomnia or refer you to a sleep specialist.

The Trillion-Transistor Chip That Just Left a Supercomputer in the Dust

By Jason Dorrier -Nov 22, 2020109

https://spkt.io/a/1297886

The history of computer chips is a thrilling tale of extreme miniaturization.

The smaller, the better is a trend that’s given birth to the digital world as we know it. So, why on earth would you want to reverse course and make chips a lot bigger? Well, while there’s no particularly good reason to have a chip the size of an iPad in an iPad, such a chip may prove to be genius for more specific uses, like artificial intelligence or simulations of the physical world.

At least, that’s what Cerebras, the maker of the biggest computer chip in the world, is hoping.

The Cerebras Wafer-Scale Engine is massive any way you slice it. The chip is 8.5 inches to a side and houses 1.2 trillion transistors. The next biggest chip, NVIDIA’s A100 GPU, measures an inch to a side and has a mere 54 billion transistors. The former is new, largely untested and, so far, one-of-a-kind. The latter is well-loved, mass-produced, and has taken over the world of AI and supercomputing in the last decade.

So can Goliath flip the script on David? Cerebras is on a mission to find out.

Big Chips Beyond AI

When Cerebras first came out of stealth last year, the company said it could significantly speed up the training of deep learning models.

Since then, the WSE has made its way into a handful of supercomputing labs, where the company’s customers are putting it through its paces. One of those labs, the National Energy Technology Laboratory, is looking to see what it can do beyond AI.

So, in a recent trial, researchers pitted the chip—which is housed in an all-in-one system about the size of a dorm room mini-fridge called the CS-1—against a supercomputer in a fluid dynamics simulation. Simulating the movement of fluids is a common supercomputer application useful for solving complex problems like weather forecasting and airplane wing design.

The trial was described in a preprint paper written by a team led by Cerebras’s Michael James and NETL’s Dirk Van Essendelft and presented at the supercomputing conference SC20 this week. The team said the CS-1 completed a simulation of combustion in a power plant roughly 200 times faster than it took the Joule 2.0 supercomputer to do a similar task.

The CS-1 was actually faster-than-real-time. As Cerebrus wrote in a blog post, “It can tell you what is going to happen in the future faster than the laws of physics produce the same result.”

The researchers said the CS-1’s performance couldn’t be matched by any number of CPUs and GPUs. And CEO and cofounder Andrew Feldman told VentureBeat that would be true “no matter how large the supercomputer is.” At a point, scaling a supercomputer like Joule no longer produces better results in this kind of problem. That’s why Joule’s simulation speed peaked at 16,384 cores, a fraction of its total 86,400 cores.

A comparison of the two machines drives the point home. Joule is the 81st fastest supercomputer in the world, takes up dozens of server racks, consumes up to 450 kilowatts of power, and required tens of millions of dollars to build. The CS-1, by comparison, fits in a third of a server rack, consumes 20 kilowatts of power, and sells for a few million dollars.

While the task is niche (but useful) and the problem well-suited to the CS-1, it’s still a pretty stunning result. So how’d they pull it off? It’s all in the design.

Cut the Commute

Computer chips begin life on a big piece of silicon called a wafer. Multiple chips are etched onto the same wafer and then the wafer is cut into individual chips. While the WSE is also etched onto a silicon wafer, the wafer is left intact as a single, operating unit. This wafer-scale chip contains almost 400,000 processing cores. Each core is connected to its own dedicated memory and its four neighboring cores.

Putting that many cores on a single chip and giving them their own memory is why the WSE is bigger; it’s also why, in this case, it’s better.

Most large-scale computing tasks depend on massively parallel processing. Researchers distribute the task among hundreds or thousands of chips. The chips need to work in concert, so they’re in constant communication, shuttling information back and forth. A similar process takes place within each chip, as information moves between processor cores, which are doing the calculations, and shared memory to store the results.

It’s a little like an old-timey company that does all its business on paper.

The company uses couriers to send and collect documents from other branches and archives across town. The couriers know the best routes through the city, but the trips take some minimum amount of time determined by the distance between the branches and archives, the courier’s top speed, and how many other couriers are on the road. In short, distance and traffic slow things down.

Now, imagine the company builds a brand new gleaming skyscraper. Every branch is moved into the new building and every worker gets a small filing cabinet in their office to store documents. Now any document they need can be stored and retrieved in the time it takes to step across the office or down the hall to their neighbor’s office. The information commute has all but disappeared. Everything’s in the same house.

Cerebras’s megachip is a bit like that skyscraper. The way it shuttles information—aided further by its specially tailored compiling software—is far more efficient compared to a traditional supercomputer that needs to network a ton of traditional chips.

Simulating the World as It Unfolds

It’s worth noting the chip can only handle problems small enough to fit on the wafer. But such problems may have quite practical applications because of the machine’s ability to do high-fidelity simulation in real-time. The authors note, for example, the machine should in theory be able to accurately simulate the air flow around a helicopter trying to land on a flight deck and semi-automate the process—something not possible with traditional chips.

Another opportunity, they note, would be to use a simulation as input to train a neural network also residing on the chip. In an intriguing and related example, a Caltech machine learning technique recently proved to be 1,000 times faster at solving the same kind of partial differential equations at play here to simulate fluid dynamics.

They also note that improvements in the chip (and others like it, should they arrive) will push back the limits of what can be accomplished. Already, Cerebras has teased the release of its next-generation chip, which will have 2.6 trillion transistors, 850,00 cores, and more than double the memory.

Of course, it still remains to be seen whether wafer-scale computing really takes off. The idea has been around for decades, but Cerebras is the first to pursue it seriously. Clearly, they believe they’ve solved the problem in a way that’s useful and economical.

Other new architectures are also being pursued in the lab. Memristor-based neuromorphic chips, for example, mimic the brain by putting processing and memory into individual transistor-like components. And of course, quantum computers are in a separate lane, but tackle similar problems.

It could be that one of these technologies eventually rises to rule them all. Or, and this seems just as likely, computing may splinter into a bizarre quilt of radical chips, all stitched together to make the most of each depending on the situation.

Image credit: Cerebras

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JASON DORRIERJason is managing editor of Singularity Hub. He did research and wrote about finance and economics before moving on to science, technology, and the future. He is curious about pretty much everything, and sad he’ll only ever know a tiny fraction of it all.Learn More

Scientists identify brain cells that drive wakefulness and resist general anesthetics

by Perelman School of Medicine at the University of Pennsylvania

Neuroscientists don’t know precisely what brain circuits control wakefulness and sleep, nor exactly how drugs for general anesthesia affect those circuits. But a new study from Penn Medicine researchers brings neuroscience a step closer to solving that important conundrum.

A team of researchers from the Perelman School of Medicine at the University of Pennsylvania, in a study published online Nov. 13 in Current Biology, identified a population of neurons in the hypothalamus region of the brain that keeps mice from sleeping when they normally would when they are activated. Activating these neurons also “wakes” them from ongoing exposure to inhaled anesthetics like isoflurane or sevoflurane, and even helps maintain the alert state when animals are dosed with anesthetics.

The study also supports a hypothesis long debated by neuroscientists: that the parts of the brain regulating sleep and waking are also capable of regulating the brain’s response to general anesthetics.

“Our findings add to evidence that the neural circuits regulating wakefulness may also be important for the exit from general anesthesia,” said study senior author Max Kelz, MD, PhD, the Anesthesia Distinguished Professor at the Perelman School of Medicine at the University of Pennsylvania.

The findings point to the possibility of future pharmaceuticals to actively speed the exit from anesthetic states and could also promote wakefulness that might be useful in neurologic diseases such as narcolepsy. In patients with the capacity to recover from minimally conscious states, therapeutics that engage strong wake-promoting systems could offer novel therapeutic strategies to coax the brain back to a state of conscious wakefulness. 

Kelz and colleagues, including the first author of the study, PhD candidate Sarah Reitz, focused on a region of the hypothalamus known as preoptic area (POA). Prior studies had yielded conflicting findings about which populations of POA neurons contribute to sleep, wakefulness, and anesthesia. However, spurred by recent findings that previously targeted populations of POA neurons are actually much more diverse on the molecular level than had been assumed, the Penn Medicine team examined one recently identified sub-population that express the tachykinin 1 gene, known as POA Tac1 neurons.

The scientists genetically engineered mice in which POA Tac1 neurons—and only those neurons—could be switched “on” for a few hours by giving the animals an injection of a harmless chemical called CNO.

“We found that activating the mice’s POA Tac1 neurons sharply increased the wakefulness of those mice compared to the control mice,” Reitz said. By using electroencephalography, or EEG, the researchers observed that in a period when the mice normally would be spending most of their time sleeping, control mice, on average, fell asleep within a few minutes of receiving an injection of an inert chemical, spending only about 40 percent of the four-hour recording session asleep. However, the CNO-injected, POA Tac1-activated mice stayed awake for nearly the entire session, experiencing only a few, brief periods of sleep. At times when the mice were active, the POA Tac1-activated mice also had much longer intervals of wakefulness compared to the control mice.

In further experiments, the researchers found that these same POA Tac1 neurons could promote wakefulness against general anesthetics—drugs that are used to keep patients in an unconscious state during major surgery. Compared to normal conditions, switching on POA Tac1 neurons increased the amount of anesthetic required to induce an unconscious state. Moreover, when these neurons were activated, mice emerged from both isoflurane- and sevoflurane-induced anesthetic states at doses that had previously kept them unconscious.

Remarkably, inhibiting POA Tac1 neurons instead of activating them had no effect on natural sleep or anesthesia-induced unconsciousness—suggesting that these neurons may be “quiet” under many conditions or that, while they are sufficient to produce wakefulness, these POA Tac1 neurons may not be always required for wakefulness. The researchers continue to study POA hypothalamic neurons to tease apart the sub-populations responsible for different sleep- and wake-related functions.

“Now that we understand the potential power of these POA Tac1 neurons, we are starting to study their firing patterns in animals as they naturally cycle through states of sleep and wakefulness, as well as enter or exit states of general anesthesia,” said Kelz. “We wonder whether poorly timed resumption of firing in these or other wake-promoting neurons might ultimately be responsible for the rare one in a thousand cases in which anesthetized patients inappropriately regain consciousness during their surgical procedures.”    

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Explore furtherCortex-wide variation of neuronal cellular energy levels depending on the sleep-wake states

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More information: Sarah L. Reitz et al. Activation of Preoptic Tachykinin 1 Neurons Promotes Wakefulness over Sleep and Volatile Anesthetic-Induced Unconsciousness, Current Biology (2020). DOI: 10.1016/j.cub.2020.10.050Journal information:Current BiologyProvided by Perelman School of Medicine at the University of Pennsylvania

MeowTalk: Alexa developer’s app to translate cat’s miaow

By Cristina Criddle
Technology reporterPublished7 hours ago

An app that aims to translate your cat’s miaow has been developed by a former Amazon Alexa engineer.

MeowTalk records the sound and then attempts to identify the meaning.

The cat’s owner also helps to label the translation, creating a database for the AI software to learn from.

Currently, there are only 13 phrases in the app’s vocabulary including: “Feed me!”, “I’m angry!” and “Leave me alone!”

Research suggests that, unlike their human servants, cats do not share a language.

Each cat’s miaow is unique and tailored to its owner, with some more vocal than others.

So, instead of a generic database for cat sounds, the app’s translation differs with each individual profile.

By recording and labelling sounds, the artificial intelligence and machine-learning software can better understand each individual cat’s voice – the more it’s used, the more accurate it can become.

The eventual aim is to develop a smart-collar, Javier Sanchez, group technical program manager at app developer Akvelon, said in a webinar on its website.

The technology would then translate your cat’s miaow instantly, and a human voice would speak through the collar.ADVERTISEMENT

“I think this is especially important now because, with all the social distancing that’s happening, you have people that are confined at home with … a significant other – this feline,” Mr Sanchez added.

“This will enable them to communicate with their cat, or at least understand their cat’s intent, and build a very important connection.”

The app is available free on both Google Play Store and Apple’s App Store.

As it’s still in its early stages of development, there are mixed reviews, with several users complaining of errors in the app.

“I’m getting quite irritated,” one review said. “I just downloaded it and haven’t even been able to use it because it just keeps telling me there is a wifi/connection error.”

“I was getting the translation ‘I’m in love!’ 90% of the time,” another user said.https://emp.bbc.com/emp/SMPj/2.36.3/iframe.htmlmedia captionCats can recognise their names when called

“While it’s nice to think that my cats love me so much, I’d caught one of my cats hissing and growling during play – and it said she was in love then too.”

But others were positive, and the app has an average rating of 4.3 on the Google Play Store.

“For now, if you don’t take it too seriously, it’s a really fun app,” one review said. “And, who knows, maybe in time, it will really learn my cat’s true meow in all instances. It surely looks promising.”

“Really cool concept and I’ve enjoyed it as my cats never stop talking,” another review added.

However, users have also expressed concern about privacy on the app over how the data from the recordings is stored and used.

In its privacy policy, the app says it is in a “development phase” and advises anyone “concerned about data retention” to uninstall the app until it is fully compliant with the EU’s GDPR privacy law

“Most cat vocalisations are actually to communicate with humans, as most owners will respond to them,” Juliette Jones, cat behaviour specialist at Wood Green, The Animals Charity, said.

As the app relies on the owner labelling translations, there is room for miscommunication, she added.

“There may be some inaccuracies which could give owners the wrong impression about what their cats are feeling.

“This could be detrimental to the cat, the owner and their relationship – for instance, if a cat is purring it doesn’t necessarily mean they are happy and restful. A purr can also be seeking affection or indicating discomfort. In its current form, the app should only be used for entertainment.”

“We will probably never be able to covert a cat’s miaow into human words,” Anita Kelsey, cat behaviourist and author of ‘Let’s Talk About Cats’, said. “All we can do is have fun thinking about what they might be saying from our own human perspective.

“The app seems like fun and there’s no harm in having fun with your cat.”

After Testing Positive (and Negative) for Covid-19, Elon Musk Contacted a Harvard Doctor. The Response Is a Master Class in Emotional Intelligence

A fascinating Twitter conversation teaches major lessons in medicine, and persuasive communication.

BY JUSTIN BARISO, AUTHOR, EQ APPLIED@JUSTINJBARISO

Elon Musk was frustrated. 

He had been experiencing mild sniffles, a cough, and a slight fever–enough symptoms to convince him to get tested for Covid-19. Musk, who obviously has more resources and greater access to medical treatment than the average person, ended up taking a total of four tests (according to the story he shared on Twitter).

“Something extremely bogus is going on,” Musk tweeted. “Two tests came back negative, two came back positive. Same machine, same test, same nurse. Rapid antigen test from BD.”

The internet was quick to respond. Some reached out to Musk to see how he was feeling. Writer Stephen King simply replied, “You’re pos.” A scientist openly mocked Musk, calling him “Space Karen” and accusing the tech CEO of not reading up on the test “before complaining to his millions of followers.”

But then something very interesting happened.

Musk decided to reach out directly to an expert in the field of communicable disease (on Twitter, of course). What followed was a master class in communication, persuasion, and emotional intelligence.

Breaking Down Barriers

Michael Mina is an immunologist, physician, and assistant professor of epidemiology at the Harvard T.H. Chan School of Public Health. He tweets regularly on the Covid-19 pandemic, breaking down complex research for easy access to the public.

Somehow, Musk stumbled across Mina’s research, and proceeded to ask him for his opinion on a specific type of Covid test. 

Mina begins his reply on a positive note (“Great question,” he exclaims). He follows that by:

• Getting into the nuances of Musk’s inquiry
• Presenting alternative scenarios, directly answering Musk’s question in the light of each one
• Offering to send Musk a more detailed answer via direct message
• Attempting to motivate Musk to act

“I think you’d be interested in the detailed answer,” Mina tells Musk. “You’re a scientist and it would be GREAT if you could help inform the world of the right answer to your question. So much confusion abounds.”https://platform.twitter.com/embed/index.html?creatorScreenName=JustinJBariso&dnt=false&embedId=twitter-widget-0&frame=false&hideCard=false&hideThread=true&id=1327786709791219712&lang=en&origin=https%3A%2F%2Fwww.inc.com%2Fjustin-bariso%2Fafter-testing-positive-and-negative-for-covid-elon-musk-contacted-a-harvard-doctor-his-response-is-a-master-class-in-emotional-intelligence.html&siteScreenName=Inc&theme=light&widgetsVersion=ed20a2b%3A1601588405575&width=550px

(You can read Mina’s full reply here.)

Mina’s reply is a masterful example of emotional intelligence, which includes the ability to break down barriers and manage the emotions of others. 

Musk hasn’t hidden the fact that he is quite skeptical of the public perception of Covid-19 and its effects. But those who follow Musk also know that he is a big fan of learning from experts in a given field. 

Mina could have blasted this previous skepticism. He could have spoken in a disparaging manner, or mocked Musk like the scientist mentioned earlier. Or he could have made the mistake many experts do, by answering the question in a way that is overly complex or difficult to understand.

Instead, Mina did the opposite. 

By commending Musk’s question, he sets the tone and encourages a respectful conversation. He provides evidence Musk is likely to respect. And Mina keeps a balanced view of himself by explaining things as simply as possible, showing he understands and can show empathy for his audience–in this case Musk, but also Musk’s millions of followers.

Finally, Mina offers to provide more time and attention to Musk if he were to reach out–but then he goes a step further. By acknowledging Musk as a scientist and kindly imploring him to spread the facts, he assumes the best in Musk, and appeals to his emotions.

This is important, because convincing someone of a truth is different from motivating them to do something about it. To truly galvanize others to action, you have to stir their emotions–penetrating deeply to affect a person’s thoughts and feelings. 

If you’re wondering if it worked, it did. Just over an hour later, Musk retweeted the entire conversation.

So, if you’re working to convince someone who is skeptical of something you believe strongly in, remember:

1. Set a respectful tone.

2. Show empathy.

3. Keep a balanced view of yourself.

4. Stir their emotions.

Do this right, and you’ll become a master communicator–and make emotions work for you, instead of against you.