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DNA says you’re related to a Viking, a medieval German Jew or a 1700s enslaved African? What a genetic match really means

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DNA says you're related to a Viking, a medieval German Jew or a 1700s enslaved African? What a genetic match really means

A genetic match to an ancient person doesn't mean you're more related genealogically.
Mark Edward Atkinson/Tetra Images via Getty Images

Shai Carmi, Hebrew University of Jerusalem and Harald Ringbauer, Max Planck Institute for Evolutionary Anthropology

In 2022, we reported the DNA sequences of 33 medieval people buried in a Jewish cemetery in Germany. Not long after we made the data publicly available, people started comparing their own DNA with that of the 14th-century German Jews, finding many “matches.” These medieval individuals had DNA fragments shared with thousands of people who have uploaded their DNA sequence to an online database, the same way you share DNA fragments with your relatives.

But what type of a relationship with a medieval person does a shared DNA fragment imply?

It turns out, not too much that will with your roots research.

We are population geneticists who work with ancient DNA. We understand how exciting it can be to find a genetic link to particular people who lived many generations ago. But these DNA matches aren't the tight ties you may be imagining. Here's how it works.

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Sequencing DNA from those who lived long ago

Ancient DNA is a new and rapidly growing field, with a Nobel Prize awarded in 2022 to Svante Pääbo for his foundational work.

Using samples taken from skull bones or teeth, aDNA researchers can sequence the DNA of people who lived as far back as 100,000 years ago. More than 10,000 ancient DNA sequences, or genomes, are currently available. These genomes, which from all corners of the world, have dramatically revolutionized scientists' understanding of human origins.

A new trend in ancient DNA is sequencing the genomes of “historical” individuals: those who have lived during the past millennium.

Examples include genomes from Sweden, Norway, Denmark, Iceland, Poland, Southeastern Europe, and London, Cambridge and Norwich in the U.K. Outside Europe, scientists have sequenced historical genomes from East Asia, the Swahili coast, South Africa, the Canary Islands, Lebanon, Machu Picchu, the Caribbean and the San Francisco Bay area. Genomes of enslaved Africans from Delaware, Maryland, South Carolina and St. Helena are also available.

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Some historical genomes belong to named individuals, Ludwig van Beethoven, the family of the last Russian czar, medieval Hungarian royals, the Lakota Sioux leader Sitting Bull and King Richard III of England.

horse-drawn wagon with two black-clad people in front, pulling coffin marked 'Richard III, 1452-1485'
The remains of King Richard III were reinterred in 2015.
Christopher Furlong via Getty Images News

How could you compare your own DNA with that of these historical people?

Several direct-to-consumer genetic testing companies, such as 23andMe, MyHeritage or Ancestry, make reading your own genome sequence simple and affordable. They compare your DNA with that of their other customers. They identify relatives who share with you long, continuous stretches of identical DNA and to you these matches – from the closest to the more distant.

After initial deliberation, 23andMe now lets customers compare their genomes with historical people. Other genetic testing companies don't yet, but passionate genealogists can take matters into their own hands. For example, the service GEDmatch lets users upload their own DNA data, along with published DNA sequences of any historical people. Once uploaded, GEDmatch will identify any user with whom you share genetic material.

two lines representing chromosomes with green, yellow and red bands along their length
A comparison of one chromosome's DNA sequence between a 14th-century German Jew and two living people who uploaded their DNA to GEDmatch. Each thin vertical bar represents one letter in the DNA sequence and is color-coded based on whether it is a match. A shared DNA fragment appears between living person 1 and the medieval person.
GEDMatch

So, what does a genetic match with a medieval person mean for your genealogy?

Surprisingly, very little.

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Where genealogy and genetics diverge

The first thing to understand is how many ancestors you have in each past generation. One generation back, you have two ancestors. Two generations back, that doubles to four. Then eight, and 16. By 30 generations ago, around the 12th century, you have over one ancestors.

Clearly, at this point, your ancestors include most people from your population who lived back then, excluding a small fraction who left no long-term descendants. This includes, if you have European origins, notable people such as Charlemagne or Edward I, but equally also people of every medieval social class. Your family tree reaches each of these ancestors through numerous lines.

a web of red lines getting denser and denser toward the top of the image, with generations marked 0 to 15 running vertically upwards
The red dot at generation 0 represents a present-day person in a simulated population of 100,000 people. Each tiny red dot represents one person, and the red lines connect people to their . Ancestors reached through multiple lines in the family tree are marked in black circles. The number of lines becomes so large so quickly that beyond 15 generations ago, most ancestors are reached by multiple lines.
Graham Coop

Mathematical research demonstrates the surprising fact. In any given population, the number of lines in your family tree that reach any specific medieval person is about the same between you and everyone else who belongs to the same population you do. In other words, everyone alive is equally related, genealogically, to all medieval people from that population.

The next step is to understand how many ancestors you actually inherit DNA from. Surprisingly again, very few.

Despite your millions or more medieval ancestors, you inherit DNA from only a tiny fraction of them. So, we're sorry, you probably didn't inherit any DNA from Charlemagne or Edward I. For example, you have only about 2,000 genetic ancestors from the 12th century. In other words, your DNA sequence is a mosaic of approximately 2,000 “fragments,” each tracing back to a single 12th-century person.

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Who are the medieval people whose DNA you inherited? Each fragment of your DNA descends from a random line up your family tree – father's mother's mother's father and so on – at each generation in the past, selecting at random one of two parents. The more lines in your family tree that reach a certain medieval person, the more likely you are to inherit DNA from that person.

family tree
For someone alive today, the number of genealogical ancestors doubles each generation. But each DNA fragment (colored bars) is inherited through a random, zigzagging path up the family tree, meaning DNA is inherited only from a small fraction of one's ancestors.
Shai Carmi, CC BY-ND

But remember, the number of family lines that reach a medieval person is about the same for all present-day individuals from a given population. Therefore, all individuals inherit DNA from any medieval person with very similar probabilities. So, sharing genetic material with one particular medieval person or another is just a matter of chance, and everyone is playing the same .

Here's an analogy. Going to a casino and rolling a roulette ball onto 24 does not mean 24 is your special number. Anyone else might have rolled 24 as well. Similarly, sharing a DNA fragment with any one out of your millions of medieval genealogical ancestors does not mean any special relationship – beyond sharing a DNA fragment.

And if you don't have a shared segment, you just didn't get lucky. It doesn't mean you're any less genealogically related to that medieval person than anyone else from your population who does have a shared segment.

As a side note, a “population” is not always well defined, but these arguments hold generally for people with similar origins.

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How to interpret a historical DNA match

Consider again the medieval German Jews. Some present-day Ashkenazi (European) Jews will share DNA with one particular medieval Jew. Some will share with another. Some will share with none. It's a lottery draw. And given that most Ashkenazi Jews today are genealogically related in a very similar way to the medieval German Jews, seeing that shared DNA fragment does not imply any unique genealogical relatedness.

On the other hand, if you're willing to consider more recent ancestors, DNA matches can be informative. The same mathematical models show that the number of family lines reaching a particular historical person living around 200 or 300 years ago will be very different across present-day people. Therefore, a DNA match with an 18th-century person implies a more specific genealogical relationship, one that most other present-day indviduals do not have.

This pattern was demonstrated in a recent 23andMe study. Comparing the genomes of 18th-century enslaved Africans from Maryland to more than 9 million of their customers, 23andMe discovered over 41,000 living relatives, including a few nearly direct descendants.

3D models of enslaved African Americans: one a teenage boy, one a woman in her 30s
Facial reconstructions based on skeletal remains of enslaved African Americans who worked at Catoctin Furnace in Maryland, where scientists have also sequenced ancient DNA.
Katherine Frey/The Washington Post via Getty Images

How far back in time does a DNA match still have genealogical meaning? For example, are DNA matches informative in the period between the late Middle Ages and the 17th century? We don't know yet. Future research will be needed to clarify this question, as well as deviations from the simple model of a single, freely mixing population.

In the meantime, as scientists rapidly accumulate more and more historical genome sequences, keep the quirky behavior of human genealogies in mind when interpreting a DNA match.The Conversation

Shai Carmi, Associate Professor of Population and Statistical Genetics, Hebrew University of Jerusalem and Harald Ringbauer, Group Leader, Department of Archaeogenetics, Max Planck Institute for Evolutionary Anthropology

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This article is republished from The Conversation under a Creative Commons license. Read the original article.

The Conversation

Human differences in judgment lead to problems for AI

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theconversation.com – Mayank Kejriwal, Research Assistant Professor of Industrial & Engineering, of Southern California – 2024-05-14 07:14:06

Bias isn't the only human imperfection turning up in AI.

Emrah Turudu/Photodisc via Getty Images

Mayank Kejriwal, University of Southern California

Many people understand the concept of bias at some intuitive level. In society, and in artificial intelligence systems, racial and gender biases are well documented.

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If society could somehow bias, would all problems go away? The late Nobel laureate Daniel Kahneman, who was a key figure in the field of behavioral economics, argued in his last book that bias is just one side of the coin. Errors in judgments can be attributed to two sources: bias and noise.

Bias and noise both play important roles in fields such as law, medicine and financial forecasting, where human judgments are central. In our work as computer and information scientists, my colleagues and I have found that noise also plays a role in AI.

Statistical noise

Noise in this context means variation in how people make judgments of the same problem or situation. The problem of noise is more pervasive than initially meets the eye. A seminal work, dating back all the way to the Great Depression, has found that different judges gave different sentences for similar cases.

Worryingly, sentencing in court cases can depend on things such as the temperature and whether the local football team won. Such factors, at least in part, contribute to the perception that the justice system is not just biased but also arbitrary at times.

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Other examples: Insurance adjusters might give different estimates for similar claims, reflecting noise in their judgments. Noise is likely present in all manner of contests, ranging from wine tastings to local beauty pageants to college admissions.

Behavioral economist Daniel Kahneman explains the concept of noise in human judgment.

Noise in the data

On the surface, it doesn't seem likely that noise could affect the performance of AI systems. After all, machines aren't affected by weather or football teams, so why would they make judgments that vary with circumstance? On the other hand, researchers know that bias affects AI, because it is reflected in the data that the AI is trained on.

For the new spate of AI models like ChatGPT, the gold standard is human performance on general intelligence problems such as common sense. ChatGPT and its peers are measured against human-labeled commonsense datasets.

Put simply, researchers and developers can ask the machine a commonsense question and compare it with human answers: “If I place a heavy rock on a paper table, will it collapse? Yes or No.” If there is high agreement between the two – in the best case, perfect agreement – the machine is approaching human-level common sense, according to the test.

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So where would noise in? The commonsense question above seems simple, and most humans would likely agree on its answer, but there are many questions where there is more disagreement or uncertainty: “Is the sentence plausible or implausible? My dog plays volleyball.” In other words, there is potential for noise. It is not surprising that interesting commonsense questions would have some noise.

But the issue is that most AI tests don't account for this noise in experiments. Intuitively, questions generating human answers that tend to agree with one another should be weighted higher than if the answers diverge – in other words, where there is noise. Researchers still don't know whether or how to weigh AI's answers in that situation, but a first step is acknowledging that the problem exists.

Tracking down noise in the machine

Theory aside, the question still remains whether all of the above is hypothetical or if in real tests of common sense there is noise. The best way to prove or disprove the presence of noise is to take an existing test, remove the answers and get multiple people to independently label them, meaning answers. By measuring disagreement among humans, researchers can know just how much noise is in the test.

The details behind measuring this disagreement are complex, involving significant statistics and math. Besides, who is to say how common sense should be defined? How do you know the human judges are motivated enough to think through the question? These issues lie at the intersection of good experimental design and statistics. Robustness is key: One result, test or set of human labelers is unlikely to convince anyone. As a pragmatic matter, human labor is expensive. Perhaps for this reason, there haven't been any studies of possible noise in AI tests.

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To address this gap, my colleagues and I designed such a study and published our findings in Nature Scientific Reports, showing that even in the domain of common sense, noise is inevitable. Because the setting in which judgments are elicited can matter, we did two kinds of studies. One type of study involved paid workers from Amazon Mechanical Turk, while the other study involved a smaller-scale labeling exercise in two labs at the University of Southern California and the Rensselaer Polytechnic Institute.

You can think of the former as a more realistic online setting, mirroring how many AI tests are actually labeled before being released for and evaluation. The latter is more of an extreme, guaranteeing high quality but at much smaller scales. The question we set out to answer was how inevitable is noise, and is it just a matter of quality control?

The results were sobering. In both settings, even on commonsense questions that might have been expected to elicit high – even universal – agreement, we found a nontrivial degree of noise. The noise was high enough that we inferred that between 4% and 10% of a system's performance could be attributed to noise.

To emphasize what this means, suppose I built an AI system that achieved 85% on a test, and you built an AI system that achieved 91%. Your system would seem to be a lot better than mine. But if there is noise in the human labels that were used to score the answers, then we're not sure anymore that the 6% improvement means much. For all we know, there may be no real improvement.

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On AI leaderboards, where large language models like the one that powers ChatGPT are , performance differences between rival systems are far narrower, typically less than 1%. As we show in the paper, ordinary statistics do not really come to the rescue for disentangling the effects of noise from those of true performance improvements.

Noise audits

What is the way forward? Returning to Kahneman's book, he proposed the concept of a “noise audit” for quantifying and ultimately mitigating noise as much as possible. At the very least, AI researchers need to estimate what influence noise might be .

Auditing AI systems for bias is somewhat commonplace, so we believe that the concept of a noise audit should naturally follow. We hope that this study, as well as others like it, to their adoption.The Conversation

Mayank Kejriwal, Research Assistant Professor of Industrial & Systems Engineering, University of Southern California

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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Iron fuels immune cells – and it could make asthma worse

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theconversation.com – Benjamin Hurrell, Assistant Professor of Research in Molecular Microbiology and Immunology, of Southern California – 2024-05-14 07:13:50

Iron carries oxygen throughout the body, but ironically, it can also make it harder to breathe for people with asthma.

Hiroshi Watanabe/Stone via Getty Images

Benjamin Hurrell, University of Southern California and Omid Akbari, University of Southern California

You've likely heard that you can get iron from eating spinach and steak. You might also know that it's an essential trace element that is a major component of hemoglobin, a protein in red blood cells that carries oxygen from your lungs to all parts of the body.

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A lesser known important function of iron is its involvement in generating energy for certain immune cells.

In our lab's newly published research, we found that blocking or limiting iron uptake in immune cells could potentially ease up the symptoms of an asthma attack caused by allergens.

Immune cells that need iron

During an asthma attack, harmless allergens activate immune cells in your lungs called ILC2s. This causes them to multiply and release large amounts of cytokines – messengers that immune cells use to communicate – and to unwanted inflammation. The result is symptoms such as coughing and wheezing that make it feel like someone is squeezing your airways.

To assess the role iron plays in how ILC2s function in the lungs, we conducted a of experiments with ILC2s in the lab. We then confirmed our findings in mice with allergic asthma and in with different severities of asthma.

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First, we found that ILC2s use a protein called transferrin receptor 1, or TfR1, to take up iron. When we blocked this protein as the ILC2s were undergoing activation, the cells were unable to use iron and could no longer multiply and cause inflammation as well as they did before.

We then used a chemical called an iron chelator to prevent ILC2s from using any iron at all. Iron chelators are like superpowered magnets for iron and are used in medical treatments to manage conditions where there's too much iron in the body.

When we deprived ILC2s with an iron chelator, the cells had to change their metabolism and switch to a different way of getting energy, like trading in a car for a bicycle. The cells weren't as effective at causing inflammation in the lungs anymore.

Person with one hand to chest and other hand clutching an inhaler

An asthma attack can feel like someone is squeezing your airways.

Mariia Siurtukova/Moment via Getty Images

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Next, we limited cellular iron in mice with sensitive airways due to ILC2s. We did this in three different ways: by inhibiting TfR1, adding an iron chelator or inducing low overall iron levels using a synthetic protein called mini-hepcidin. Each of these methods helped reduce the mice's airway hyperreactivity – basically reducing the severity of their asthma symptoms.

Lastly, we looked at cells from patients with asthma. We noticed something interesting: the more TfR1 protein on their ILC2 cells, the worse their asthma symptoms. In other words, iron was playing a big role in how bad their asthma got. Blocking TfR1 and administering iron chelators both reduced ILC2 proliferation and cytokine production, suggesting that our findings in mice apply to human cells. This means we can move these findings from the lab to clinical trials as quickly as possible.

Iron therapy for asthma

Iron is like the conductor of an orchestra, instructing immune cells such as ILC2s how to behave during an asthma attack. Without enough iron, these cells can't cause as much trouble, which could mean fewer asthma symptoms.

Next, we're working on targeting a patient's immune cells during an asthma attack. If we can lower the amount of iron available to ILC2s without depleting overall iron levels in the body, this could mean a new therapy for asthma that tackles the root cause of the disease, not just the symptoms. Available treatments can control symptoms to keep patients alive, but they are not curing the disease. Iron-related therapies may offer a better solution for patients with asthma.

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Our discovery applies to more than just asthma. It could be a -changer for other diseases where ILC2s are involved, such as eczema and type 2 diabetes. Who knew iron could be such a big deal to your immune system?The Conversation

Benjamin Hurrell, Assistant Professor of Research in Molecular Microbiology and Immunology, University of Southern California and Omid Akbari, Professor of Molecular Microbiology and Immunology, University of Southern California

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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‘Dancing’ raisins − a simple kitchen experiment reveals how objects can extract energy from their environment and come to life

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theconversation.com – Saverio Eric Spagnolie, Professor of Mathematics, of Wisconsin-Madison – 2024-05-13 07:29:32

Surface bubble growth can lift objects upward against gravity.

Saverio Spagnolie

Saverio Eric Spagnolie, University of Wisconsin-Madison

Scientific discovery doesn't always require a high-tech laboratory or a hefty budget. Many people have a first-rate lab right in their own homes – their kitchen.

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The kitchen offers plenty of opportunities to view and explore what physicists call soft matter and complex fluids. Everyday phenomena, such as Cheerios clustering in milk or rings left when drops of coffee evaporate, have led to discoveries at the intersection of physics and chemistry and other tasteful collaborations between food scientists and physicists.

Two students, Sam Christianson and Carsen Grote, and I published a new study in Nature Communications in May 2024 that dives into another kitchen observation. We studied how objects can levitate in carbonated fluids, a phenomenon that's whimsically referred to as dancing raisins.

The study explored how objects like raisins can rhythmically move up and down in carbonated fluids for several minutes, even up to an hour.

An accompanying Twitter thread about our research went viral, amassing over half a million views in just two days. Why did this particular experiment catch the imaginations of so many?

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Bubbling physics

Sparkling and other carbonated beverages fizz with bubbles because they contain more gas than the fluid can – they're “supersaturated” with gas. When you open a bottle of champagne or a soft drink, the fluid pressure drops and CO₂ molecules begin to make their escape to the surrounding .

Bubbles do not usually form spontaneously in a fluid. A fluid is composed of molecules that like to stick together, so molecules at the fluid boundary are a bit unhappy. This results in surface tension, a force which seeks to reduce the surface area. Since bubbles add surface area, surface tension and fluid pressure normally squeeze any forming bubbles right back out of existence.

But rough patches on a container's surface, like the etchings in some champagne glasses, can protect new bubbles from the crushing effects of surface tension, offering them a chance to form and grow.

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Bubbles also form inside the microscopic, tubelike cloth fibers left behind after wiping a glass with a towel. The bubbles grow steadily on these tubes and, once they're big enough, detach and float upward, carrying gas out of the container.

But as many champagne enthusiasts who put fruits in their glasses know, surface etchings and little cloth fibers aren't the only places where bubbles can form. Adding a small object like a raisin or a peanut to a sparkling drink also enables bubble growth. These immersed objects act as alluring new surfaces for opportunistic molecules like CO₂ to accumulate and form bubbles.

And once enough bubbles have grown on the object, a levitation act may be performed. Together, the bubbles can lift the object up to the surface of the liquid. Once at the surface, the bubbles pop, dropping the object back down. The then begins again, in a periodic vertical dancing motion.

Dancing raisins

Raisins are particularly good dancers. It takes only a few seconds for enough bubbles to form on a raisin's wrinkly surface before it starts to rise upward – bubbles have a harder time forming on smoother surfaces. When dropped into just-opened sparkling water, a raisin can dance a vigorous tango for 20 minutes, and then a slower waltz for another hour or so.

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Anyone with a few kitchen staples can do their own dancing raisins experiment.

We found that rotation, or spinning, was critically important for coaxing large objects to dance. Bubbles that cling to the bottom of an object can keep it aloft even after the top bubbles pop. But if the object starts to spin even a little bit, the bubbles underneath make the body spin even faster, which results in even more bubbles popping at the surface. And the sooner those bubbles are , the sooner the object can get back to its vertical dancing.

Small objects like raisins do not rotate as much as larger objects, but instead they do the twist, rapidly wobbling back and forth.

Modeling the bubbly flamenco

In the paper, we developed a mathematical model to predict how many trips to the surface we would expect an object like a raisin to make. In one experiment, we placed a 3D-printed sphere that acted as a model raisin in a glass of just-opened sparkling water. The sphere traveled from the bottom of the container to the top over 750 times in one hour.

The model incorporated the rate of bubble growth as well as the object's shape, size and surface roughness. It also took into account how quickly the fluid loses carbonation based on the container's geometry, and especially the flow created by all that bubbly activity.

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Small objects covered in bubbles in carbonated water move upwards towards the surface and back down.

Bubble-coated raisins ‘dance' to the surface and plummet once their lifting agents have popped.

Saverio Spagnolie

The mathematical model helped us determine which forces influence the object's dancing the most. For example, the fluid drag on the object turned out to be relatively unimportant, but the ratio of the object's surface area to its volume was critical.

Looking to the future, the model also provides a way to determine some hard to measure quantities using more easily measured ones. For example, just by observing an object's dancing frequency, we can learn a lot about its surface at the microscopic level without to see those details directly.

Different dances in different theaters

These results aren't just interesting for carbonated beverage lovers, though. Supersaturated fluids exist in nature, too – magma is one example.

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As magma in a volcano rises closer to the Earth's surface, it rapidly depressurizes, and dissolved gases from inside the volcano make a dash for the exit, just like the CO₂ in carbonated water. These escaping gases can form into large, high-pressure bubbles and emerge with such force that a volcanic eruption ensues.

The particulate matter in magma may not dance in the same way raisins do in soda water, but tiny objects in the magma may affect how these explosive play out.

The past decades have also seen an eruption of a different kind – thousands of scientific studies devoted to active matter in fluids. These studies look at things such as swimming microorganisms and the insides of our fluid-filled cells.

Most of these active systems do not exist in water but instead in more complicated biological fluids that contain the energy necessary to produce activity. Microorganisms absorb nutrients from the fluid around them to continue swimming. Molecular motors carry cargo along a superhighway in our cells by pulling nearby energy in the form of ATP from the environment.

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Studying these systems can scientists learn more about how the cells and bacteria in the human body function, and how on this planet has evolved to its current state.

Meanwhile, a fluid itself can behave strangely because of a diverse molecular composition and bodies moving around inside it. Many new studies have addressed the behavior of microorganisms in such fluids as mucus, for instance, which behaves like both a viscous fluid and an elastic gel. Scientists still have much to learn about these highly complex systems.

While raisins in soda water seem fairly simple when compared with microorganisms swimming through biological fluids, they offer an accessible way to study generic features in those more challenging settings. In both cases, bodies extract energy from their complex fluid environment while also affecting it, and fascinating behaviors ensue.

New insights about the physical world, from geophysics to biology, will continue to emerge from tabletop-scale experiments – and perhaps from right in the kitchen.The Conversation

Saverio Eric Spagnolie, Professor of Mathematics, University of Wisconsin-Madison

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This article is republished from The Conversation under a Creative Commons license. Read the original article.

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