A drop of food coloring slowly spreading in a glass of water is driven by a process known as diffusion. While the mathematics of diffusion have been known for many years, how this process works in living organisms is not as well understood.
Now, a study published in Nature Communications provides new insights on the process of diffusion in complex systems. The result of a collaboration between physicists at Penn, the University of Chile, and Heinrich Heine University Düsseldorf, this new theoretical framework has broad implications for active surfaces, such as ones found in biofilms, active coatings, and even mechanisms for pathogen clearance.
Diffusion is described by Fick’s laws: Particles, atoms, or molecules will always move from a region of high to low concentration. Diffusion is one of the most important ways that molecules move within the body. However, for the transport of big objects over large distances, standard diffusion becomes too slow to keep up.
“That’s when you need active components to help transport things around,” says study co-author Arnold Mathijssen. In biology, these actuators include cytoskeletal motors that move cargo vesicles in cells, or cilia that pump liquid out of human lungs. When many actuators accumulate on a surface, they are known as “active carpets.” Together, they can inject energy into a system in order to help make diffusion more efficient.
Mathijssen, whose research group studies the physics of pathogens, first became interested in this topic while studying biofilms with Francisca Guzmán-Lastra, an expert on the physics of active matter, and theoretical physicist Hartmut Löwen. Biofilms are another example of active carpets since they use their flagella to create “flows” that pump liquid and nutrients from their environment. Specifically, the researchers were interested in understanding how biofilms are able to sustain themselves when access to nutrients is limited. “They can increase their food uptake by creating flows, but this also costs energy. So, the question was: How much energy do you put in to get energy out?” says Mathijssen.
But studying active carpets is difficult because they don’t align neatly with Fick’s laws, so the researchers needed to develop a way to understand diffusion in these non-equilibrium systems, or ones that have added energy. “We thought that we could generalize these laws for enhanced diffusion, when you have systems that do not follow Fick’s laws but may still follow a simple formula that is widely applicable to many of these active systems,” Mathijssen says.
After figuring out how to connect the math needed to understand both bacterial dynamics and Fick’s laws, the researchers developed a model similar to the Stokes-Einstein equation, which describes the relationship with temperature and diffusion, and found that microscopic fluctuations could explain the changes they saw in particle diffusion. Using their new model, the researchers also found that the diffusion generated by these small movements is incredibly efficient, allowing bacteria to use just a small amount of energy to gain a large amount of food.
“We’ve now derived a theory that predicts the transport of molecules inside cells or close to active surfaces. My dream would be that these theories would be applied in different biophysical settings,” says Mathijssen. His new research lab at Penn will start working on follow-up experiments to test out these new models. They plan to study active diffusion both in biological and engineered microscopic systems.
Mathijssen, who is also involved on a project related to the spread of COVID-19 in food-processing facilities, says that the cilia in lungs are another important example of active carpets in biology, especially since they serve as the first line of defense against pathogens like COVID-19. He says, “That would be another very important thing to test, whether this theory of active carpets may be linked to the theory of pathogen clearance in the airways.”
Story Source:
Materials provided by University of Pennsylvania. Original written by Erica K. Brockmeier. Note: Content may be edited for style and length.

Teenagers are more likely to get hooked on marijuana, stimulants and other recreational drugs than college-aged or older adults.Adolescents and teenagers who experiment with marijuana and prescription drugs are more likely to get hooked on them than young people who try these drugs for the first time when they are college-aged or older, according to a new analysis of federal data.The research suggests that young people may be particularly vulnerable to the intoxicating effects of certain drugs, and that early exposure might prime their brains to desire them. The findings have implications for public health policymakers, who in recent years have called for increased screening and preventive measures to reverse a sharp rise in marijuana vaping among teenagers.The new study, published in JAMA Pediatrics and led by a team of scientists at the National Institute on Drug Abuse, sought to gain a better understanding of how adolescent brains respond to a variety of recreational drugs. Previous research suggested that early exposure to marijuana, nicotine and alcohol might lead to faster development of substance use disorders. But the new analysis cast a wider net, looking at the effects of nine different drugs, including opioid painkillers, stimulants, marijuana, alcohol, cigarettes, cocaine, heroin, methamphetamine and tranquilizers.The researchers used data from the government’s National Survey on Drug Use and Health, a closely watched annual study that tracks substance use and mental health issues among Americans. The new research focused on two age groups: adolescents between the ages of 12 and 17, and young adults aged 18 to 25. Alcohol was by far the most commonly used substance in both groups: A quarter of adolescents and 80 percent of young adults said they had used it. About half of young adults said they had tried cannabis or tobacco. But among adolescents, that number was smaller: Roughly 15 percent said they had experimented with cannabis, and 13 percent said they had tried tobacco.Most troubling to the authors of the new study was how many people went on to develop a substance use disorder, indicating that their experimentation had spiraled into an addiction. The researchers found that within a year of first trying marijuana, 11 percent of adolescents had become addicted to it, compared to 6.4 percent of young adults. Even more striking was that within three years of first trying the drug, 20 percent of adolescents became dependent on it, almost double the number of young adults.Adolescents who tried prescription drugs were also more likely to become addicted. About 14 percent of adolescents who took prescription stimulants for recreational use went on to develop a substance use disorder within one year, compared to just 4 percent of young adults. And while 7 percent of young adults who tried opioid painkillers became addicted soon after taking them, that figure rose to 11.2 percent among younger users.For alcohol and tobacco, however, there was not much of a difference between the two age groups: Both older and younger youth had a similar rate of developing a substance use disorder. And for illicit drugs such as cocaine and heroin, the number of adolescents using them was too small for the researchers to draw any meaningful conclusions.One possible explanation for the findings is that young people who have a greater predisposition to developing an addiction may be more likely to seek out illicit drugs at an earlier age. But Dr. Nora Volkow, a senior author of the new study and the director of NIDA, said it is known that cannabis and other drugs can have a potent effect on adolescent brains because they are still developing. Younger brains exhibit greater plasticity, or ability to change, than the relatively static brains of older individuals. As a result, drugs like cannabis are more likely to alter synaptic connections in younger brains, leading to stronger memories of pleasure and reward.“It’s a learning process when you become addicted,” said Dr. Volkow. “It’s a type of memory that gets hard-wired into your brain. That occurs much faster in an adolescent brain.”Studies show that regularly using marijuana can affect cognition in adolescents, leading to impairments in parts of the brain that are involved in learning, reasoning and paying attention. Yet in recent years the booming popularity of e-cigarettes has led to a sharp increase in the number of adolescents who vape nicotine and marijuana, a trend that has alarmed public health officials. Some studies suggest that adolescents may also be more likely to try marijuana as more and more states legalize its recreational use.Dr. Volkow said that as states implement new marijuana regulations, policymakers should work on measures aimed at protecting adolescents. She stressed that pediatricians and dentists should screen for drug use in their young patients by asking them about it. And she cautioned parents not to dismiss marijuana use in teens and adolescents as something that is harmless.“As it relates to marijuana, the drugs that were available when parents today were teenagers are very different from the drugs that are available now,” she said. “The content of THC is much higher, and the higher the THC content, the greater the risk of adverse effects.”

California continued its uneven progress in reopening schools on Monday, as elementary students began to return to classrooms in Long Beach, the state’s fourth-largest district with 70,000 students.Public schools in the state’s top three districts by enrollment — Los Angeles, San Diego and Fresno — have said they will begin to allow grade-school students back onto campus later in April, as new coronavirus cases have fallen sharply across California.Schools in Oakland and San Francisco also are scheduled to reopen next month for elementary and special-needs students. But labor agreements in both cities have allowed substantial numbers of teachers to opt out, leaving some schools without enough teachers to reopen and prompting others to scramble for substitutes.Although many smaller California districts have been open for months, large urban districts on the West Coast generally have lagged behind their counterparts in the rest of the nation. Surging infections in Southern California after the winter holiday were partly to blame for a slow rebound in the Los Angeles school system.Teachers’ unions generally are more powerful in Democratic-led Washington, Oregon and California than in many other states, and teachers have been wary of returning to what they regard as a hazardous workplace, despite federal guidance that elementary schools in particular are safe when health precautions are followed.The Long Beach school district has been able to open earlier than other large California school systems because labor unions there agreed last summer to reopen as soon as health conditions permitted, and because the city was able to start vaccinating teachers earlier than other districts in the state.Unlike most other cities in Los Angeles County, Long Beach has its own public health department, giving the city its own vaccine supplies and the power to set its own vaccine priorities, at a time when the county as a whole was making teachers wait until after other groups, like residents 65 and older, were vaccinated.“A city with its own health department has the ability to be more nimble,” said Jill Baker, the city’s schools superintendent, who called the return to classrooms this week “exciting and momentous.”The school district is among the city’s largest employers, and two-thirds of its students qualify for free or reduced-price lunches, so vaccinating school employees and reopening classrooms was viewed as economically important, Ms. Baker said.About 14,000 students in Long Beach from transitional kindergarten through fifth grade will return this week to school buildings for masked, sanitized and socially distanced instruction. They will be on a hybrid schedule, with students spending about 2½ hours at school each day, five days a week, and completing the school day with remote instruction.In-person classes for older students are scheduled to resume April 19, with grades 6 to 8 getting the option to return on April 20 and grades 9 to 11 on April 26. The last day of school will be in mid-June.

It’s not uncommon for people who experience a concussion to have moderate to severe headaches in the weeks after the injury. A new study has found a combination of two drugs, both common anti-nausea medications, given intravenously in the emergency room may relieve those headaches better than a placebo. The study is published in the March 24, 2021, online issue of Neurology®, the medical journal of the American Academy of Neurology.
Metoclopramide is an anti-nausea medicine sometimes used to treat migraine. Diphenhydramine is a common antihistamine that when used in its injected form can treat motion sickness. Higher doses of metoclopramide given intravenously can cause restlessness, so this study combined diphenhydramine with metoclopramide to prevent those symptoms.
“The headaches you get after a trauma like a fall, an assault or car accident can linger for months or even years and lead to a reduced quality of life, so the results of our study are promising,” said study author Benjamin W. Friedman, M.D., of Albert Einstein College of Medicine, Bronx, N.Y.
The study involved 160 people who experienced a head trauma and then visited an emergency room because of a headache within 10 days. They were randomly assigned to two groups: 81 people were given 20 milligrams (mg) of metoclopramide and 25 mg of diphenhydramine intravenously. The remaining 79 people were given an injection of saline solution as a placebo.
Researchers asked people to rate the intensity of their pain on a scale of zero to 10 one hour after the medication was administered. On this scale, zero means no pain and 10 means the worst pain imaginable.
The study found that the drug combination reduced the average person’s pain level by more than five points one hour later. People in the group given the combination of metoclopramide and diphenhydramine said they improved, on average, by 5.2 points on the pain scale. People in the group given a placebo, on average, said their pain improved by 3.8 points on the pain scale.
In the group given the drug combination, 43% experienced side effects like drowsiness, restlessness or diarrhea. In the group given the placebo, 28% of the people reported those kinds of side effects.
“More research is needed to determine the most effective dose of metoclopramide, and how long to administer it, to see if people can get longer-term relief after they leave the emergency room,” Friedman said. “Also, future work may be able to determine whether early treatment with this medication can target other disruptive symptoms you may get after a head injury, like depression, sleep disorders and anxiety.”
A limitation of the study is that the study participants came from high poverty areas of the country, and may have had less access to care. Because successful headache treatment may be associated with access to care, these results may not apply to the general population.
Story Source:
Materials provided by American Academy of Neurology. Note: Content may be edited for style and length.

A Japanese research group combined motion analysis that uses smartphone application and machine learning that uses an anomaly detection method, thereby developing a technique to easily screen for carpal tunnel syndrome. Carpal tunnel syndrome is common amongst middle-aged women. The disease causes compressed nerves in the wrist, causing numbness and difficulty with finger movements. While an accurate diagnosis can be reached with nerve conduction study, this is not widely used because it requires expensive devices and specialized skills. Thus, a simple screen tool that does not require any specialized knowledge or techniques is desired.
The research group of Dr. Koji Fujita of Tokyo Medical and Dental University and associate professor Yuta Sugiura of Keio University focused on increasingly poor movements of the thumb with the advancement of the disease, and analyzed its characteristics. They developed a game application for smartphones that is played using the thumbs and prepared a program that acquires the trajectory of the thumb during a game play and estimates the possibility of the disease with machine learning. The application can screen for possible carpal tunnel syndrome using a simple game that can be played in 30 sec — 1 minute. Even without gathering patient data, they were able to effectively construct an estimate mode from the data of 12 asymptomatic participants using the anomaly detection method. When this program was applied to 15 new asymptomatic subjects and 36 patients with carpal tunnel syndrome to verify its accuracy, the result was promising with 93% sensitivity, 69% specificity, and 0.86 Area Under the Curve (AUC)(1). This is equivalent or better than the results of physical examinations by expert orthopedic surgeons.
The developed tool can be used to screen for possible carpal tunnel syndrome at sites where no expert is present, such as at home or at a health center. In the future, the research group aims to develop a system that is able to encourage an examination by an expert when the disease is suspected in order to prevent exacerbation. It would prevent inconvenience and social loss associated with exacerbation of a disease, which is more common among women, and contribute to creating a society where women play an active role.
The research was conducted as part of JST’s Strategic Basic Research Program, Precursory Research for Embryonic Science and Technology (PRESTO).
(1) Area Under the Curve (AUC)
This assessment item is used for each test method, and a higher value indicates a better test. Sensitivity is the ratio of correct positive results for subjects with a disease. Specificity is the ratio of correct negative results for subjects without a disease. AUC is the comprehensive assessment indicator of accuracy that combines sensitivity and specificity and takes a value between 0 and 1.
Story Source:
Materials provided by Japan Science and Technology Agency. Note: Content may be edited for style and length.

Hail severity will increase in most regions of the world while Australia and Europe are expected to experience more hailstorms as a result of climate change, an international review led by a UNSW Sydney researcher has found.
The review study, published in Nature Reviews Earth & Environment, examined the effects climate change will have on hail in the future.
It shows a global summary of hail trends from past observations and projected future trends from simulations and models.
The review led to the general expectation that hailstorm frequency will decrease in East Asia and North America, while increasing in Australia and Europe, and that hailstorm severity will increase in most regions.
Researchers from University of Bern, Central Michigan University, Karlsruhe Institute of Technology, University of Illinois, Colorado State University and Peking University took part in the study.
“We came to the conclusion that on balance, the hail threat is likely to increase in Australia, especially in Australia’s south-east including the Sydney area,” lead author and postdoctoral researcher at UNSW Sydney’s Climate Change Research Centre, Tim Raupach said.

A combination of esophageal brushing and extensive genetic sequencing of the sample collected can detect chromosome alterations in people with Barrett’s Esophagus, identifying patients at risk for progressing to esophageal cancer, according to a new study by researchers at the Johns Hopkins Kimmel Cancer Center and Case Western Reserve University.
In Barrett’s Esophagus (BE), chronic acid reflux from the stomach damages the cells lining the lower esophagus, causing them to become more like cells of the lower digestive system. Cells in the lower esophagus progress through several precancerous stages before sometimes developing into esophageal adenocarcinoma, a cancer with a five-year survival rate below 20 percent. BE is the only known precursor to esophageal adenocarcinoma.
Clinicians can detect these progressive states in BE by looking for chromosomal alterations known as aneuploidy — a common feature in most cancer cells — but until now the process has involved multiple biopsies.
A single esophageal brushing paired with the sequencing technique called RealSeqS is sensitive and specific enough to identify aneuploidy at several stages of BE progression, and can even match specific types of aneuploidy with specific stages of the disease, the researchers say.
“Aneuploidy has long been implicated in the development, initiation or progression of esophageal cancer but the assays or experimental methods to detect this have not been as easily achieved or as high throughput as we would have wanted to allow for clinical implementation,” says senior study author Chetan Bettegowda, M.D., Ph.D., Jennison and Novak Families Professor of Neurosurgery at the Kimmel Cancer Center.
The method could help clinicians identify people at higher risk of having BE progress to esophageal adenocarcinoma, “instituting more intensive follow-up for those patients or instituting treatments at earlier stages of the disease,” Bettegowda says.

The coronavirus most likely emerged in bats before spreading to humans through another animal, according to a report to be released by the World Health Organization on Tuesday, offering some clues on a question that has become politically fraught amid accusations of interference from Beijing.According to the report on the origin of the pandemic, which was obtained by The New York Times in advance of its release, a team of experts who recently visited the Chinese city of Wuhan, where the coronavirus was first detected in late 2019, also dismissed the idea that the virus might have leaked accidentally from a Chinese laboratory as “extremely unlikely.”Officials in the United States and elsewhere have expressed concern about China’s efforts to reshape the narrative about the outbreak in Wuhan, which the authorities initially tried to conceal.Critics have assailed the inquiry by the W.H.O. team as insufficient, saying the global health agency has been too deferential to Beijing. Chinese scientists, many of whom are affiliated with the government, helped oversee the inquiry, and the report was repeatedly delayed amid delicate negotiations with Chinese officials. For months, China sought to delay the visit of the investigators in an apparent attempt to avoid scrutiny of its early mistakes in handling the pandemic.The Chinese government has defended its approach, saying it is fully cooperating with the W.H.O.In the 123-page report, the scientists outlined several theories that might explain how the virus first spread to humans. The findings in the document were first reported on Monday by The Associated Press.The report was written jointly by a team of 17 scientists from around the world and 17 Chinese scientists. The experts led a fact-finding visit to Wuhan for 27 days in January and February.During the visit to Wuhan, Chinese officials refused to share raw data about some of the earliest possible virus cases with the W.H.O. team, frustrating some of the visiting scientists.China’s lack of transparency as well as other concerns prompted a small group of scientists not affiliated with the World Health Organization to call this month for a new inquiry into the origin of the pandemic. They said such an inquiry should consider the possibility that the virus escaped from a laboratory in Wuhan or infected someone inside it.The lab leak theory has been promoted by some officials in the Trump administration, including Dr. Robert Redfield, the former director of the Centers for Disease Control and Prevention, in comments to CNN last week. He offered no evidence and emphasized that it was his opinion; the theory has been widely dismissed by scientists and U.S. intelligence officials.Matt Apuzzo contributed reporting.

The coronavirus most likely emerged in bats before spreading to humans through another animal, according to a report to be released by the World Health Organization on Tuesday, offering some clues on a question that has become politically fraught amid accusations of interference from Beijing.According to the report on the origin of the pandemic, which was obtained by The New York Times in advance of its release, a team of experts who recently visited the Chinese city of Wuhan, where the coronavirus was first detected in late 2019, also dismissed the idea that the virus might have leaked accidentally from a Chinese laboratory as “extremely unlikely.”Officials in the United States and elsewhere have expressed concern about China’s efforts to reshape the narrative about the outbreak in Wuhan, which the authorities initially tried to conceal.Critics have assailed the inquiry by the W.H.O. team as insufficient, saying the global health agency has been too deferential to Beijing. Chinese scientists, many of whom are affiliated with the government, helped oversee the inquiry, and the report was repeatedly delayed amid delicate negotiations with Chinese officials. For months, China sought to delay the visit of the investigators in an apparent attempt to avoid scrutiny of its early mistakes in handling the pandemic.The Chinese government has defended its approach, saying it is fully cooperating with the W.H.O.In the 123-page report, the scientists outlined several theories that might explain how the virus first spread to humans. The findings in the document were first reported on Monday by The Associated Press.The report was written jointly by a team of 17 scientists from around the world and 17 Chinese scientists. The experts led a fact-finding visit to Wuhan for 27 days in January and February.During the visit to Wuhan, Chinese officials refused to share raw data about some of the earliest possible virus cases with the W.H.O. team, frustrating some of the visiting scientists.China’s lack of transparency as well as other concerns prompted a small group of scientists not affiliated with the World Health Organization to call this month for a new inquiry into the origin of the pandemic. They said such an inquiry should consider the possibility that the virus escaped from a laboratory in Wuhan or infected someone inside it. The lab leak theory has been promoted by some officials in the Trump administration, including Dr. Robert Redfield, the former director of the Centers for Disease Control and Prevention, in comments to CNN last week. He offered no evidence and emphasized that it was his opinion; the theory has been widely dismissed by scientists and U.S. intelligence officials.Matt Apuzzo contributed reporting.

Bioengineering researchers at Lehigh University have identified a previously unknown interaction between receptors in human cells and the spike, or “S,” protein of SARS-CoV-2, the virus that causes COVID-19. This new information could aid in the development of new strategies to block SARS-CoV-2 entry into human cells.
X. Frank Zhang and Wonpil Im knew from recent studies that the interaction between the SARS-CoV-2 spike protein and angiotensin-converting enzyme 2 (ACE2) receptors in human cells is stronger than the interaction between the structurally identical spike protein of SARS-CoV-1, the virus that caused the 2002-2004 SARS outbreak, and the same receptors.
“Our goal was to characterize SARS-CoV-2 and study the protein-protein interactions during its invasion of human cells to provide more insights into the mechanisms that make this first step in its successful invasion process possible,” says Zhang, an associate professor in Bioengineering and Mechanical Engineering & Mechanics at Lehigh.
Their findings appear in an article called “Biomechanical characterization of SARS-CoV-2 spike RBD and human ACE2 protein-protein interaction” in a special issue of Biophysical Journal, “Biophysicists Address Covid-19 Challenges I,” published in mid-March. Additional authors include, from Lehigh University: Wenpeng Cao, Decheng Hou and Seonghan Kim in bioengineering; Chuqiao Dong in mechanical engineering and mechanics; and, from Lindsley F. Kimball Research Institute, New York Blood Center, Wanbo Tai and Lanying Du.
Using combined single-molecule force spectroscopy and molecular dynamics simulations, Zhang’s and Im’s teams were able to identify a previously unknown interaction between ACE2 glycans (sugar groups attached to the surface of proteins) and the SARS-CoV-2 spike. It is this interaction that appears to be responsible for the strengthening of the virus-cell interaction. This may partially explain the higher infection rate of COVID-19 compared to the similar virus that caused the 2002-2004 SARS outbreak, they say.
“We were surprised to find that the specific interaction between ACE2 glycans and the SARS-CoV-2 spike protein is what makes the separation of the virus from cells so difficult,” says Im, who is a professor of bioengineering, computer science, chemistry and biological sciences, as well as the Presidential Endowed Chair in Health, Science and Engineering at Lehigh.
To arrive at these findings, the team employed Zhang’s innovative single-molecule detection technique, measuring the detachment force of the spike protein-ACE2 receptor interaction. Using the all-atom molecular dynamics simulations of the complex system available in CHARMM-GUI developed by Im, they then identified the detailed structural information in this interaction.
“After we carefully removed all of the ACE2 glycans and measured the force of the interaction, we saw that the strength of the SARS-CoV-2 spike-ACE2 interaction fell back to levels similar to SARS-CoV-1,” says Zhang.
“It is possible that this newly-discovered interaction with ACE2 glycans could be a contributing factor to the higher rates of COVID-19 than the structurally similar SARS-CoV-1, which has a weaker interaction,” says Zhang. “Our hope is that researchers may be able to use this information to develop new strategies to identify, prevent, treat and vaccinate against COVID-19.”
Story Source:
Materials provided by Lehigh University. Original written by Lori Friedman. Note: Content may be edited for style and length.