Culture

Researchers at the National Institute of Standards and Technology (NIST) have found a way to link measurements made by a device integral to microchip fabrication and other industries directly to the recently redefined International System of Units (SI, the modern metric system). That traceability can greatly increase users' confidence in their measurements because the SI is now based entirely on fundamental constants of nature.

The device, a dime-size disk called a quartz crystal microbalance (QCM), is critically important to businesses that rely on precision control of the formation of thin films. Very thin: They range from micrometers (millionths of a meter) to a few tens of nanometers (billionths of a meter, or about 10,000 times thinner than a human hair) and are typically produced in a vacuum chamber by exposing a target surface to a meticulously regulated amount of chemical vapor that sticks to the surface and forms the film. The greater the exposure, the thicker the film.

Thin films are essential components in electronic semiconductor devices, optical coatings for lenses, LEDs, solar cells, magnetic recording media for computing, and many other technologies. They are also employed in technologies that measure the concentration of microbial contaminants in air, pathogens in the water supply, and the number of microorganisms that attach themselves to biological surfaces in the course of infection.

All those uses demand extremely accurate measurements of the film's thickness. Because that is difficult to measure directly, manufacturers frequently use QCMs, which have a valuable property: When an alternating current is applied to them, they vibrate at a resonant frequency unique to each disk and its mass.

To determine exactly how much film material is being deposited, they place the a QCM disk in the vacuum chamber and measure its resonant frequency. Then the disk is exposed to a chemical vapor. The more vapor that adheres to the QCM, the greater its mass -- and the slower it vibrates. That change in frequency is a sensitive measure of the added mass.

"But despite ubiquitous implementation of QCMs throughout industry and academia," said NIST physicist and lead researcher Corey Stambaugh, "a direct link to the SI unit of mass has not existed." The relationship between the SI unit of mass (the kilogram) and resonance frequency is assumed to be well characterized after decades of QCM measurements. But over the years, industry has made inquiries to NIST regarding the absolute mass accuracy of these frequency measurements. The new results presented by Stambaugh and colleagues are in large measure a response to those queries.

"We expect that our findings will enable a new, higher level of assurance in QCM measurements by providing traceability to the new SI," said NIST physicist Joshua Pomeroy, who with Stambaugh and others report their findings today in the journal Metrologia. The redefinition of the SI units in May 2019 eliminated the previous metal prototype kilogram as a standard and instead defined the kilogram in terms of a quantum constant.

In the new SI, mass at the kilogram level will be realized in the United States using that constant in NIST's Kibble balance.

In the new SI, NIST They have also developed a standard instrument, called the electrostatic force balance (EFB), that provides extremely accurate measurement of masses in the milligram range and lower), which are directly linked to the SI by way of a quantum constant. The EFB provided the team with reference milligram sized-masses with a precision on the order of a fraction of a microgram (1/1,000,000th of 1 gram, or about one millionth the mass of an average paper clip).

Stambaugh and colleagues carefully weighed an uncoated quartz disk, then suspended it in a vacuum chamber and measured its resonant frequency. About 0.5 meters (20 inches) below the disk was a furnace that heated a quantity of gold to 1480 C (2700 F). Gold vapor from the furnace rose and attached itself to the lower surface of the QCM, increasing its mass and thus slowing its resonant frequency. The scientists repeated the procedure at different time intervals and thus different amounts of mass accretion. was repeated at different time intervals. The researchers deposited gold vapor was over different time intervals and recorded the subsequent changes in resonant frequency. They weighed the disk again using the same EFB reference masses. This provided an accurate measurement of the change in mass, and thus provided an exact measure of the amount of gold deposited.

In the course of the work, the team also performed a complete assessment of the uncertainties in the QCM measurements. They identified the most accurate mathematical method of correlating the addition of mass to the change in the QCM's resonant frequency.

"This work provides a key step in a technique for traceably tracking -- and thus correcting for -- mass changes over time," said NIST physicist Zeina Kubarych.

In that regard, the new findings could help improve the way mass is disseminated following the new SI definition. The new kilogram is "realized" -- converted from an abstract definition to a physical reality -- through highly controlled laboratory measurements in a vacuum chamber. But the working standards of the kilogram will be disseminated -- physically delivered to measurement-science laboratories -- in the form of metal masses in the open air. That means that water vapor and whatever else is in the air can adsorb onto the surface of a kilogram working standard, causing inaccurate measurement of its mass.

Because humidity and air contaminants differ substantially around the world, measurements of a carefully calibrated mass standard can differ appreciably from place to place at the levels of accuracy needed for industrial and scientific metrology. If, however, a calibrated QCM were to accompany each standard, it could provide an accurate measure of the amount of material adsorbed in transit and at the destination, helping the labs to receive more accurate definitions of the new kilogram while taking environmental conditions into account.

While many immunologists use mouse models to conduct their research, J. Oriol Sunyer of Penn's School of Veterinary Medicine has made transformational scientific insights using a very different creature: rainbow trout.

In a paper featured on the cover of the journal Science Immunology, Sunyer and colleagues developed a method to manipulate the trout immune system to reveal a new understanding of how the animals defend against infection while promoting a healthy microbiome. The work addresses a decades-old question of whether mucosal antibodies--those present on mucosal surfaces of the body such as the gut, or in the case of fish, the gills--evolved to fight pathogens, or to preserve a healthy microbiome. As it turns out, mucosal immunoglobulins coevolved both roles from very early on during vertebrate evolution.

"You might be thinking, 'Rainbow trout? We fish for them; we eat them,'" says Sunyer. "But it turns out they can also tell us a lot about some fundamental biomedical, evolutionary, and immunological questions."

Specifically, Sunyer and colleagues found that a mucosal antibody, an immunoglobulin known as IgT, is critical both in controlling pathogens and in regulating the microbiome of fish gills, a tissue type that shares similarities with several mucosal surfaces of mammals, such as the intestines.

"We found that IgT is playing two paradoxical roles--on the one hand reducing bad microbes, and on the other hand promoting the presence of certain beneficial bacteria," says Sunyer. "Fish are the earliest bony vertebrates to possess a mucosal immune system, and so the fact that fish possess a specialized immunoglobulin that does both jobs suggests that these two processes are so fundamentally important for vertebrate survival that they arose concurrently, early on in evolution."

For nearly 20 years, Sunyer's lab has contributed a steady stream of discovery regarding the evolution and roles of the immune system using fish as model species. In 2010, a seminal paper in Nature Immunology featured on the journal cover identified the role of IgT. It was the first time that fish were shown to have a form of mucosal immunity--a more specialized response to pathogens that enter the body from the environment; in this case, through the gills, skin, and fish gut.

"Before that we thought only four-legged animals, or tetrapods, had mucosal immunity," Sunyer says. That study demonstrated the induction of potent IgT responses upon infection with a mucosal pathogen.

The group also showed that IgT coats a large portion of the bacteria that are part of the fishes' microbiome, the community of bacteria and other microbes that dwell on various tissues of the animals' bodies. That got the researchers thinking about which function arose first for vertebrate mucosal immunoglobulins: fighting pathogens or preserving a healthy microbiome.

"In mammals, the immunoglobulin IgA seems to have analogous function to IgT in fish," Sunyer explains. "In the last few years there have been some key studies showing that IgA is required to keep the mammalian microbiome in check. In mice and humans lacking IgA, their microbiome changes: The beneficial bacteria go down and the potentially disease-causing bacteria go up."

A weakness of these studies in mammals lacking IgA, Sunyer notes, is the inability to tease apart the precise role of IgA in preserving a balanced microbiome, since the lack of IgA from birth precludes the establishment of a healthy microbiota in these animals.

To better understand the roles of mucosal immunoglobulins in preserving a healthy microbiome, Sunyer and colleagues developed a model in adult fish where researchers could temporarily deplete them of IgT, lasting about two months.

By doing so they could study the role of IgT in preserving, rather than establishing, a healthy microbiome, while also evaluating the susceptibility to pathogens of fish lacking IgT.

When they depleted IgT, the researchers found that levels of a mucosal parasite greatly increased, underscoring the immunoglobulin's role in defending against harmful invaders. But they also saw a dramatic impact on the microbiome composition: IgT-depleted fish lost the IgT coating on the bacterial community in their gills and had more bacteria "escape" from gill surfaces and enter the tissue layer beneath, leading to tissue damage and inflammation.

Looking closely at the bacteria coated by IgT in normal animals, the research team found that IgT targeted specific species over others. These species included bacteria associated with both health and disease states in fish--similar to what had been found with IgA in mammals.

Critically, the authors found that the overall microbiome in IgT-depleted fish was significantly altered, in a shift known as dysbiosis. The overall diversity of bacteria present decreased, numbers of beneficial bacteria such as those producing short-chain fatty acids--critical for the maintenance of tissue integrity and immune homeostasis--also decreased, while disease-associated species increased.

"We see that there seems to be specific microbes that have to be controlled," says Sunyer. "Either they are harmful and tend to escape and cause problems in the nearby tissue in the absence of IgT, or perhaps they are beneficial but require IgT to colonize the mucosal surfaces. In both fish and mammals, it now seems apparent that their respective mucosal immunoglobulins do these jobs."

One great benefit of the researcher's IgT depletion technique is that it's temporary and performed in adult animals. After several weeks of depletion, the fish IgT levels return to normal. Thus the researchers were able to track the microbiome as IgT came back, observing what amounted to recovery; the microbes in the gill regained IgT coating, the microbiome was restored to its initial composition, and the tissue damage and inflammation that had been seen around the gills was reversed.

"In microbiome studies, recovery is a very important point," Sunyer says. "When you take an antibiotic, you can perturb your microbiome to the extent that recovery may take a very long time, but the perturbation we used, of removing IgT, had a profound but transient effect on the microbiome composition, which underwent a speedy recovery."

As more and more scientific studies identify links between the microbiome and various aspects of health from maintaining a healthy weight to the risk of cancer or even neurological conditions like Alzheimer's and schizophrenia, Sunyer is hopeful that his fish model will find even more applications.

"Studying only mammalian models is not going to be enough to understand the role of the microbiome in all of these physiological processes," says Sunyer.

Because the symbiotic relationship between vertebrates and their microbiome is very ancient, and one which first flourished with the emergence of mucosal immunoglobulins in fish, Sunyer says that "rainbow trout will help us discover the underlying mechanisms by which the interactions between immunoglobulins and the microbiome influence immunity, metabolism, cancer, and much more."

These studies, Sunyer adds, will have a crucial impact on the potential uses of specific species of fish bacteria as probiotic agents that may stimulate the immune system to protect against pathogens. With every other fish that we eat deriving from fish farming, an industry plagued with emerging pathogens, novel therapies, such as probiotics, are in urgent need.

Microelectronics like semiconductor devices are at the heart of the technologies we use each day. As we move into an era where we are stretching the limits of Moore’s Law, it is essential to find new ways to continue to pack more circuitry into each individual device in order to increase the speed and capability of our computers.

Researchers at the U.S. Department of Energy’s (DOE) Argonne National Laboratory have developed a new technique that could potentially help make these increasingly small but complex devices. The technique, known as molecular layer etching, is detailed in a new paper published in Chemistry of Materials.

“MLE has the potential to help usher in new pathways for fabricating and controlling material geometries at the nanoscale, which could open new doors in microelectronics and extend beyond traditional Moore’s Law scaling.” — Jeff Elam, Argonne chemist

To make microelectronics smaller, manufacturers have to cram in more and more circuitry onto smaller films and 3D structures. Today, this happens by using thin film deposition and etching, techniques to grow or remove films one layer at a time.

“Our ability to control matter at the nanoscale is limited by the kinds of tools we have to add or remove thin layers of material. Molecular layer etching (MLE) is a tool to allow manufacturers and researchers to precisely control the way thin materials, at microscopic and nanoscales, are removed,” said lead author Matthias Young, an assistant professor at the University of Missouri and former postdoctoral researcher at Argonne.

Together with molecular layer deposition (MLD), a deposition technique, MLE can be used to design microscopic architectures. These approaches are analogs of atomic layer deposition (ALD) and atomic layer etching (ALE), the more commonly applied techniques for fabricating microelectronics. However, unlike atomic layering techniques, which deal exclusively with inorganic films, MLD and MLE can be used to grow and remove organic films as well.

How it works

In principle, MLE works by exposing thin films, several nanometers or micrometers thick, to pulses of gas inside a vacuum chamber. The process starts with one gas (Gas A) which, upon entry, reacts with the surface of the film. Next, the film is exposed to a second gas (Gas B).  This AB process is repeated until the desired thickness is removed from the film.

“The net effect of A and then B is the removal of a molecular layer from your film,” said Argonne chemist Jeff Elam, a co-author of the study. “If you do that process sequentially, over and over again, you can reduce the thickness of your film to achieve the desired final thickness.”

A key aspect of MLD is that the A and B surface reactions are self-limiting.  They only continue until all of the available reactive surface sites are consumed, and then the reactions naturally terminate.  This self-limiting behavior is extremely helpful in manufacturing since it is relatively easy to scale the process up to larger substrate sizes. 

Researchers tested their approach using alucone, an organic material similar to silicone rubber that has potential applications in flexible electronics. Gas A in their experiment was a lithium-containing salt, and Gas B was trimethyl aluminum (TMA), an organometallic aluminum-based compound.

During the etching process, the lithium compound reacted with the surface of the alucone film in a way that caused the lithium to stick onto the surface and disrupt the chemical bonding in the film. Then, when the TMA was introduced and reacted, it removed the layer of film containing lithium.  The lithium serves a sacrificial role — it is deposited on the surface temporarily to break chemical bonds but is then removed by the TMA.

“The process can go on layer by layer like that and you can remove the whole material if you wanted to,” Young said.

Opening new doors in microelectronics

Using this technique can help manufacturers and researchers develop new ways of making nanostructures. The process may also be a safer option for them to use because it is free of halogens, a harsh components of chemicals common in other etching processes. It also has the advantage of being selective; the etching technique can selectively remove MLD layers without affecting nearby ALD layers.

“MLE has the potential to help usher in new pathways for fabricating and controlling material geometries at the nanoscale, which could open new doors in microelectronics and extend beyond traditional Moore’s Law scaling,” Elam said.

A system created by MIT researchers could be used to automatically update factual inconsistencies in Wikipedia articles, reducing time and effort spent by human editors who now do the task manually.

Wikipedia comprises millions of articles that are in constant need of edits to reflect new information. That can involve article expansions, major rewrites, or more routine modifications such as updating numbers, dates, names, and locations. Currently, humans across the globe volunteer their time to make these edits.

In a paper being presented at the AAAI Conference on Artificial Intelligence, the researchers describe a text-generating system that pinpoints and replaces specific information in relevant Wikipedia sentences, while keeping the language similar to how humans write and edit.

The idea is that humans would type into an interface an unstructured sentence with updated information, without needing to worry about style or grammar. The system would then search Wikipedia, locate the appropriate page and outdated sentence, and rewrite it in a humanlike fashion. In the future, the researchers say, there's potential to build a fully automated system that identifies and uses the latest information from around the web to produce rewritten sentences in corresponding Wikipedia articles that reflect updated information.

"There are so many updates constantly needed to Wikipedia articles. It would be beneficial to automatically modify exact portions of the articles, with little to no human intervention," says Darsh Shah, a PhD student in the Computer Science and Artificial Intelligence Laboratory (CSAIL) and one of the lead authors. "Instead of hundreds of people working on modifying each Wikipedia article, then you'll only need a few, because the model is helping or doing it automatically. That offers dramatic improvements in efficiency."

Many other bots exist that make automatic Wikipedia edits. Typically, those work on mitigating vandalism or dropping some narrowly defined information into predefined templates, Shah says. The researchers' model, he says, solves a harder artificial intelligence problem: Given a new piece of unstructured information, the model automatically modifies the sentence in a humanlike fashion. "The other [bot] tasks are more rule-based, while this is a task requiring reasoning over contradictory parts in two sentences and generating a coherent piece of text," he says.

The system can be used for other text-generating applications as well, says co-lead author and CSAIL graduate student Tal Schuster. In their paper, the researchers also used it to automatically synthesize sentences in a popular fact-checking dataset that helped reduce bias, without manually collecting additional data. "This way, the performance improves for automatic fact-verification models that train on the dataset for, say, fake news detection," Schuster says.

Shah and Schuster worked on the paper with their academic advisor Regina Barzilay, the Delta Electronics Professor of Electrical Engineering and Computer Science and a professor in CSAIL.

Neutrality masking and fusing

Behind the system is a fair bit of text-generating ingenuity in identifying contradictory information between, and then fusing together, two separate sentences. It takes as input an "outdated" sentence from a Wikipedia article, plus a separate "claim" sentence that contains the updated and conflicting information. The system must automatically delete and keep specific words in the outdated sentence, based on information in the claim, to update facts but maintain style and grammar. That's an easy task for humans, but a novel one in machine learning.

For example, say there's a required update to this sentence (in bold): "Fund A considers 28 of their 42 minority stakeholdings in operationally active companies to be of particular significance to the group." The claim sentence with updated information may read: "Fund A considers 23 of 43 minority stakeholdings significant." The system would locate the relevant Wikipedia text for "Fund A," based on the claim. It then automatically strips out the outdated numbers (28 and 42) and replaces them with the new numbers (23 and 43), while keeping the sentence exactly the same and grammatically correct. (In their work, the researchers ran the system on a dataset of specific Wikipedia sentences, not on all Wikipedia pages.)

The system was trained on a popular dataset that contains pairs of sentences, in which one sentence is a claim and the other is a relevant Wikipedia sentence. Each pair is labeled in one of three ways: "agree," meaning the sentences contain matching factual information; "disagree," meaning they contain contradictory information; or "neutral," where there's not enough information for either label. The system must make all disagreeing pairs agree, by modifying the outdated sentence to match the claim. That requires using two separate models to produce the desired output.

The first model is a fact-checking classifier -- pretrained to label each sentence pair as "agree," "disagree," or "neutral" -- that focuses on disagreeing pairs. Running in conjunction with the classifier is a custom "neutrality masker" module that identifies which words in the outdated sentence contradict the claim. The module removes the minimal number of words required to "maximize neutrality" -- meaning the pair can be labeled as neutral. That's the starting point: While the sentences don't agree, they no longer contain obviously contradictory information. The module creates a binary "mask" over the outdated sentence, where a 0 gets placed over words that most likely require deleting, while a 1 goes on top of keepers.

After masking, a novel two-encoder-decoder framework is used to generate the final output sentence. This model learns compressed representations of the claim and the outdated sentence. Working in conjunction, the two encoder-decoders fuse the dissimilar words from the claim, by sliding them into the spots left vacant by the deleted words (the ones covered with 0s) in the outdated sentence.

In one test, the model scored higher than all traditional methods, using a technique called "SARI" that measures how well machines delete, add, and keep words compared to the way humans modify sentences. They used a dataset with manually edited Wikipedia sentences, which the model hadn't seen before. Compared to several traditional text-generating methods, the new model was more accurate in making factual updates and its output more closely resembled human writing. In another test, crowdsourced humans scored the model (on a scale of 1 to 5) based on how well its output sentences contained factual updates and matched human grammar. The model achieved average scores of 4 in factual updates and 3.85 in matching grammar.

Removing bias

The study also showed that the system can be used to augment datasets to eliminate bias when training detectors of "fake news," a form of propaganda containing disinformation created to mislead readers in order to generate website views or steer public opinion. Some of these detectors train on datasets of agree-disagree sentence pairs to "learn" to verify a claim by matching it to given evidence.

In these pairs, the claim will either match certain information with a supporting "evidence" sentence from Wikipedia (agree) or it will be modified by humans to include information contradictory to the evidence sentence (disagree). The models are trained to flag claims with refuting evidence as "false," which can be used to help identify fake news.

Unfortunately, such datasets currently come with unintended biases, Shah says: "During training, models use some language of the human written claims as "give-away" phrases to mark them as false, without relying much on the corresponding evidence sentence. This reduces the model's accuracy when evaluating real-world examples, as it does not perform fact-checking."

The researchers used the same deletion and fusion techniques from their Wikipedia project to balance the disagree-agree pairs in the dataset and help mitigate the bias. For some "disagree" pairs, they used the modified sentence's false information to regenerate a fake "evidence" supporting sentence. Some of the give-away phrases then exist in both the "agree" and "disagree" sentences, which forces models to analyze more features. Using their augmented dataset, the researchers reduced the error rate of a popular fake-news detector by 13 percent.

"If you have a bias in your dataset, and you're fooling your model into just looking at one sentence in a disagree pair to make predictions, your model will not survive the real world," Shah says. "We make models look at both sentences in all agree-disagree pairs."

Many of the microbes that live in your gut are also found in your stool, and fecal microbiota transplants (FMTs) are being studied to determine whether they can improve health outcomes in patients with various diseases such as ulcerative colitis and Crohn's disease. However, it is important to recognize that FMT does carry some risk such as bloodstream infections and the transmission of drug-resistant bacteria. Furthermore, FMT treatment for most microbiome-associated diseases has not been rigorously studied in humans--and any such studies would be subject to regulation by the Food and Drug Administration. In a pair of forums publishing February 12 in the journal Cell Host & Microbe, clinicians and an FDA scientist detail some areas of FMT research that could facilitate the development of safe and effective FMT therapies for patients.

Currently, the FDA has stated that it intends to exercise enforcement discretion regarding the investigational new drug (IND) requirements for the use of FMT to treat Clostridioides difficile infections not responsive to standard therapies, provided that the treating physician obtains adequate informed consent. This means that, while the treatment is not yet approved, it is sometimes used in this particular situation without submitting an IND to the FDA. Investigators or practitioners who are using FMT to treat other diseases or conditions still need to submit an IND to the FDA. In addition, researchers are evaluating different preparations of FMT including autologous FMT and material provided by stool banks. Also, several manufacturers are developing FMT with the goal of licensure. "We are excited about the opportunity to move the fecal microbiota transplant field forward, particularly where FMT may represent an opportunity to improve outcomes for patients," says Kate Markey (@katemarkey), a hematology physician at the Memorial Sloan Kettering Cancer Center and corresponding author of one of the forums.

At this time, the methods to collect and prepare the donated material are not sophisticated, and the optimal FMT product characteristics, such as the best bacterial composition for a specific outcome, are not known. The FDA is working to provide stakeholders information about donor screening and testing and manufacturing considerations for FMT. "While this information is routinely communicated by the FDA during public scientific meetings, we hope this forum provides a mechanism to provide this information to a broader audience," says Paul Carlson, an FDA principal investigator in the Laboratory of Mucosal Pathogens and Cellular Immunology and corresponding author of the other forum. "We want to give an overview of FDA regulation of fecal microbiota for transplantation and lay out some considerations for investigators to help ensure the safety of patients and the viability of the bacteria in the transplanted material."

These considerations include a reference list of potential pathogens for donor screening to exclude donors with a high risk of pathogen exposure. Further, Dr. Carlson provides considerations for manufacturing processes and controls, such as the use of anaerobic chambers during FMT manufacturing to preserve potentially useful bacteria that may be highly sensitive to oxygen. At this time, given the lack of knowledge about the optimal bacterial composition of FMT used to treat a particular disease, loss of these anerobic organisms may negatively impact effectiveness.

The authors say that placebo controlled clinical trials of FMT to treat a particular disease are important to demonstrate safety and effectiveness and advance the scientific understanding of FMT. "The next steps are further clinical trials with the array of products either now available or in development. As current trials reach completion, the true potential of this therapy will become clear," says Markey.

While there is still much work to be done before we see mainstream usage of FMT, Dr. Carlson says that the "FDA is engaged and continues to work with people conducting clinical trials using FMT."

A common variation in a human gene that affects the brain's reward processing circuit increases vulnerability to the rewarding effects of the main psychoactive ingredient of cannabis in adolescent females, but not males, according to preclinical research by Weill Cornell Medicine investigators. As adolescence represents a highly sensitive period of brain development with the highest risk for initiating cannabis use, these findings in mice have important implications for understanding the influence of genetics on cannabis dependence in humans.

The brain's endocannabinoid system regulates activity of cannabinoids that are normally produced by the body to influence brain development and regulate mood, as well as those from external sources, such as the psychoactive ingredient THC, also known as Δ9-tetrahydrocannabinol, which is found in cannabis. An enzyme called fatty acid amide hydrolase (FAAH) breaks down a cannabinoid called anandamide that is naturally found in the brain and is most closely related to THC, helping to remove it from circulation.

In the study, published Feb. 12 in Science Advances, the investigators examined mice harboring a human gene variant that causes FAAH to degrade more easily, increasing overall anandamide levels in the brain. They discovered that the variant resulted in an overactive reward circuit in female--but not male adolescent mice--that resulted in higher preference for THC in females. Previous clinical studies linked this FAAH variant with increased risk for problem drug use, but no studies had specifically looked at the mechanistic effect on cannabis dependence.

"Our study shows that a variant in the FAAH gene, which is found in about one-third of people, increases vulnerability to THC in females and has large-scale impact on brain regions and pathways responsible for processing reward," said lead author Dr. Caitlin Burgdorf, a recent doctoral graduate from the Weill Cornell Graduate School of Medical Sciences. "Our findings suggest that genetics can be a contributing factor for increased susceptibility to cannabis dependence in select populations."

The team found that female mice with the FAAH variant showed an increased preference for the environment in which they'd been exposed to THC over a neutral environment when they were exposed to the substance during adolescence, and the effect persisted into adulthood. However, if female mice with this variant were exposed to THC for the first time in adulthood, there was no increased preference for THC. These findings in mice parallel observations in humans that a select population of females are more sensitive to the effects of cannabis and demonstrate a quicker progression to cannabis dependence. "Our findings suggest that we have discovered a genetic factor to potentially identify subjects at risk for cannabis dependence," said Dr. Burgdorf.

The investigators also found that the genetic variant led to increased neuronal connections and neural activity between two regions of the brain heavily implicated in reward behavior. Next, the team reversed the overactive reward circuit in female mice and found that decreasing circuit activity dampened the rewarding effects of THC.

As substance abuse disorders often emerge during adolescence, the investigators say this study has significant implications for translating these findings to inform developmental and genetic risk factors for human cannabis dependence.

"Our study provides new insights into cannabis dependence and provides us with a circuit and molecular framework to further explore the mechanisms of cannabis dependence," said co-senior author Dr. Anjali Rajadhyaksha, professor of neuroscience in pediatrics and associate professor of neuroscience in the Feil Family Brain and Mind Research Institute and a member of the Drukier Institute for Children's Health at Weill Cornell Medicine.

Although genetic factors are increasingly found to be associated with risk for other types of addiction, very few studies have investigated genetic factors associated with increasing risk for cannabis dependence. "In the future, we could use the presence of this FAAH genetic variant to potentially predict if an individual is more likely to be vulnerable to cannabis dependence," said co-senior author, Dr. Francis Lee, chair of the Department of Psychiatry at Weill Cornell Medicine and psychiatrist-in-chief at NewYork-Presbyterian/Weill Cornell Medical Center. "We are getting one step closer to understanding exactly how neurodevelopmental and genetic factors play interrelated roles to increase susceptibility for cannabis dependence."

There are numerous articles on how friendships change in your 20s, 30s, and after marriage or parenthood. What we don't know is how ubiquitous these changes are throughout the animal kingdom. Researchers from Archbold Biological Station describe the social lives of Florida Scrub-Jays in different stages of life in the journal PeerJ on February 10, 2020.

Florida Scrub-Jays are monogamous cooperative breeders that mate for life. In most birds, after the offspring leave the nest they disperse to breed on their own. In Florida Scrub-Jays, the young delay dispersal, remaining with their parents to help rear their younger siblings for the next few years. They are known as helpers.

Lead author Dr. Angela Tringali, along with co-authors that included two post-baccalaureate research interns, found that these helpers associate with many more individuals than breeders. "If helpers want to become breeders, they need their own territory and mate. In addition to helping their parents, they make forays away from home, presumably looking for available territories and potential mates. This increases the number of other birds that helpers associate with and the helpers' importance in connecting individuals with one another," explains Tringali. Whether a bird was a breeder or helper explained 38% of the variation in the number of individual "associates" among birds and 48% of its 'cliquishness', the tendency to associate with a set of individuals all of whom are directly associated.

In 2018, a year marked by unusually low reproductive success at Archbold, where the demography of Florida Scrub-Jays has been studied for 50 years, some breeders did not nest, and those that did nest began later in the year. In this year, breeders socialized with far more birds, much like the helpers. Without nests or young that needed care, breeders chose to interact with other individuals outside of their immediate family, in a manner similar to helpers, suggesting that social interactions are more important than simply finding a new mate.

The authors conclude that an individual's strategy for success changes with its life stage. As helpers, individuals explore to find a territory and mate, but once found, the priority shifts to defending their territory and provisioning offspring. But even for breeders, when time permits, socialization beyond the family group is important. "We have tended to frame foray behavior strictly as a strategy for finding a territory or mate, but this analysis demonstrates that when not tending an active nest, breeders also will foray beyond their territories. Maintaining extra-group relationships may reduce the costs of territory defense, predation risk, or the time spent in vigilance, and enhance knowledge of the status of neighboring territories," noted Dr. Reed Bowman, Research Director of the Avian Ecology Program at Archbold Biological Station.

The authors note that these conclusions are based on 'snapshots in time' collected by scientists visiting sampling points near the intersection of scrub-jay territory boundaries twice per week. Next, the plan is to get a more complete picture of where, when, and with whom the birds are interacting. Dr. Bowman says, "We are completing a pilot project tracking scrub-jays tagged with a new technology of transmitters whose signals are received by a grid of receivers. We will know the exact location of multiple scrub-jays throughout the day, which will enable us to answer questions about social interactions in more detail and better understand habitat use, movement, and dispersal."

What The Studies Did: These two related studies and editorial examined the association of sexual orientation and gender identity with a history of self-reported skin cancer.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

Authors: Arash Mostaghimi, M.D., M.P.A., M.P.H., of Brigham and Women's Hospital and Harvard Medical School in Boston, is the corresponding author of both studies.

(doi:10.1001/jamadermatol.2019.4196 and 10.1001/jamadermatol.2019.4197)

Editor's Note: Please see the articles for additional information, including other authors, author contributions and affiliations, conflicts of interest and financial disclosures, and funding and support.

Hookworms infect nearly around 700 million people in the world, mostly in countries where sanitation is poor, and people often walk barefoot.

The body's immune system is critical to attacking the hookworm, but these parasites are masters of escape and individuals typically remain infected throughout their lifetime, often resulting in death or complications stemming from anaemia.

Monash University researchers have uncovered a key way that hookworms evade the immune system - providing new hope in the search for a vaccine.

Importantly, the researchers, led by Professor Nicola Harris from Monash University's Central Clinical School, may have discovered why people are unable to kill hookworms.

The research, published today in the leading journal, Cell Host and Microbe, shows that a type of immune cell in the blood, called neutrophils, can kill hookworms by releasing neutrophil extracellular traps (NETs) made up of toxin-coated DNA.

However, the hookworm has developed a way to sense what the neutrophil is doing, releasing an enzyme that degrades the DNA backbone of the trap, allowing the hookworm to remain and continue infecting its host.

Professor Harris and her colleagues suggest the NETS created by the neutrophils could kill the worm providing people living in hookworm prone areas by boosting much needed immunity.

Professor Harris says that the discovery could form the basis of a vaccine to achieve this goal.

"No protective vaccines currently exist, and their successful development requires an improved understanding of both the body's immune response and the biology of these worm-like pests known as nematodes," Professor Harris said.

"We have found that hookworms have evolved a previously unrecognised evasion mechanism to degrade the immune system's response, thus persistently infecting their hosts.

"We may now be able to look at new vaccination approaches that target the enzyme secreted by the hookworm parasite to alleviate infestation and to decrease the likelihood of reinfection."

Boston, MA -- In the largest study of skin cancer rates among gay, lesbian or bisexual individuals, investigators from Brigham and Women's Hospital report important differences in skin cancer prevalence among sexual minorities. Rates of skin cancer were higher among gay and bisexual men compared to heterosexual men but lower among bisexual women than heterosexual women. These findings, which were possible because of the sexual orientation and gender identity (SOGI) module built into a national system of surveys, have implications for patient education and community outreach initiatives focused on reducing skin cancer risk. They also have implications for the design of future nationwide surveys. Results are published in JAMA Dermatology.

"It's absolutely critical that we ask about sexual orientation and gender identity in national health surveys; if we never ask the question, we'd never know that these differences exist," said corresponding author Arash Mostaghimi, MD, MPA, MPH, director of the Dermatology Inpatient Service at the Brigham. "This information helps inform the nation about how to allocate health resources and how to train providers and leaders. When we look at disparities, it may be uncomfortable, but we need to continue to ask these questions to see if we're getting better or worse at addressing them. Historically, this kind of health variation was hidden, but we now recognize that it's clinically meaningful."

Mostaghimi and colleagues leveraged data from the Behavioral Risk Factor Surveillance System (BRFSS), using data collected from annual questionnaires from 2014 to 2018. The Centers for Disease Control (CDC) uses the BRFSS to collect information about risk factors and behaviors among adults. About 450,000 adults are interviewed by telephone by the BRFSS each year. Beginning in 2014, the BRFSS began using the SOGI module to include questions about sexual orientation and gender identity. This module was administered in 37 states.

Mostaghimi and colleagues compared skin cancer rates among heterosexual men to rates in gay or bisexual men and compared rates among heterosexual women to lesbian or bisexual women. Rates of skin cancer were 8.1 percent among gay men and 8.4 percent among bisexual men, statistically higher than the rate of 6.7 percent among heterosexual men. Skin cancer rates were 5.9 percent among lesbian women and 6.6 percent among heterosexual women, which was not a statistically significant difference. However, the rate of 4.7 percent among bisexual women was statistically significantly lower than heterosexual women.

The authors note that the data are based on self-reported skin cancer diagnoses, which have not been confirmed by a physician. The SOGI module was also only implemented in 37 states, so may not be generalizable to all states.

The BRFSS survey did not collect information about risk factors for skin cancer, such as UV exposure, Fitzpatrick skin type (a measure of skin color and susceptibility to sun burn), HIV status and more. However, smaller studies have reported higher usage of indoor tanning beds among sexual minority men, a known risk factor for skin cancer.

The CDC recently considered stopping implementation of the SOGI module for future BRFSS surveys, a move Mostaghimi feels would hinder efforts to support this population.

"This is the first time we've been able to look nationally at data about skin cancer rates among sexual minorities. Eliminating SOGI would prevent us from better studying this vulnerable population over time to see how rates may change from year to year," said Mostaghimi. "As a next step, we want to connect with sexual minority communities to help identify the cause of these differences in skin cancer rates. This is work that will need to be done thoughtfully but may help not just sexual minorities but everyone."

Scientists have discovered hundreds of unusually large, bacteria-killing viruses with capabilities normally associated with living organisms, blurring the line between living microbes and viral machines.

These phages -- short for bacteriophages, so-called because they "eat" bacteria -- are of a size and complexity considered typical of life, carry numerous genes normally found in bacteria and use these genes against their bacterial hosts.

University of California, Berkeley, researchers and their collaborators found these huge phages by scouring a large database of DNA that they generated from nearly 30 different Earth environments, ranging from the guts of premature infants and pregnant women to a Tibetan hot spring, a South African bioreactor, hospital rooms, oceans, lakes and deep underground.

Altogether they identified 351 different huge phages, all with genomes four or more times larger than the average genomes of viruses that prey on single-celled bacteria.

Among these is the largest bacteriophage discovered to date: Its genome, 735,000 base-pairs long, is nearly 15 times larger than the average phage. This largest known phage genome is much larger than the genomes of many bacteria.

"We are exploring Earth's microbiomes, and sometimes unexpected things turn up. These viruses of bacteria are a part of biology, of replicating entities, that we know very little about," said Jill Banfield, a UC Berkeley professor of earth and planetary science and of environmental science, policy and management, and senior author of a paper about the findings appearing Feb 12 in the journal Nature. "These huge phages bridge the gap between non-living bacteriophages, on the one hand, and bacteria and Archaea. There definitely seem to be successful strategies of existence that are hybrids between what we think of as traditional viruses and traditional living organisms."

Ironically, within the DNA that these huge phages lug around are parts of the CRISPR system that bacteria use to fight viruses. It's likely that once these phages inject their DNA into bacteria, the viral CRISPR system augments the CRISPR system of the host bacteria, probably mostly to target other viruses.

"It is fascinating how these phages have repurposed this system we thought of as bacterial or archaeal to use for their own benefit against their competition, to fuel warfare between these viruses," said UC Berkeley graduate student Basem Al-Shayeb. Al-Shayeb and research associate Rohan Sachdeva are co-first authors of the Nature paper.

New Cas protein

One of the huge phages also is able to make a protein analogous to the Cas9 protein that is part of the revolutionary tool CRISPR-Cas9 that Jennifer Doudna of UC Berkeley and her European colleague, Emmanuelle Charpentier, adapted for gene-editing. The team dubbed this tiny protein CasØ, because the Greek letter Ø, or phi, has traditionally been used to denote bacteriophage.

"In these huge phages, there is a lot of potential for finding new tools for genome engineering," Sachdeva said. "A lot of the genes we found are unknown, they don't have a putative function and may be a source of new proteins for industrial, medical or agricultural applications."

Aside from providing new insight into the constant warfare between phages and bacteria, the new findings also have implications for human disease. Viruses, in general, carry genes between cells, including genes that confer resistance to antibiotics. And since phages occur wherever bacteria and Archaea live, including the human gut microbiome, they can carry damaging genes into the bacteria that colonize humans.

"Some diseases are caused indirectly by phages, because phages move around genes involved in pathogenesis and antibiotic resistance," said Banfield, who is also director of microbial research at the Innovative Genomics Institute (IGI) and a CZ Biohub investigator. "And the larger the genome, the larger the capacity you have to move around those sorts of genes, and the higher the probability that you will be able to deliver undesirable genes to bacteria in human microbiomes."

Sequencing Earth's biomes

For more than 15 years, Banfield has been exploring the diversity of bacteria, Archaea -- which, she says, are fascinating cousins of bacteria -- and phages in different environments around the planet. She does this by sequencing all the DNA in a sample and then piecing the fragments together to assemble draft genomes or, in some cases, fully curated genomes of never-before-seen microbes.

In the process, she has found that many of the new microbes have extremely tiny genomes, seemingly insufficient to sustain independent life. Instead, they appear to depend on other bacteria and archaea to survive.

One year ago, she reported that some of the largest phages, a group she called Lak phages, can be found in our guts and mouths, where they prey on gut and saliva microbiomes.

The new Nature paper came out of a more thorough search for huge phages within all the metagenomic sequences Banfield has accumulated, plus new metagenomes provided by research collaborators around the globe. The metagenomes came from baboons, pigs, Alaskan moose, soil samples, oceans, rivers, lakes and groundwater, and included Bangladeshis who had been drinking arsenic-tainted water.

The team identified 351 phage genomes that were more than 200 kilobases long, four times the average phage genome length of 50 kilobytes (kb). They were able to establish the exact length of 175 phage genomes; the others could be much larger than 200 kb. One of the complete genomes, 735,000 base-pairs long, is now the largest known phage genome.

While most of the genes in these huge phages code for unknown proteins, the researchers were able to identify genes that code for proteins critical to the machinery, called the ribosome, that translates messenger RNA into protein. Such genes are not typically found in viruses, only in bacteria or archaea.

The researchers found many genes for transfer RNAs, which carry amino acids to the ribosome to be incorporated into new proteins; genes for proteins that load and regulate tRNAs; genes for proteins that turn on translation and even pieces of the ribosome itself.

"Typically, what separates life from non-life is to have ribosomes and the ability to do translation; that is one of the major defining features that separate viruses and bacteria, non-life and life," Sachdeva said. "Some large phages have a lot of this translational machinery, so they are blurring the line a bit."

Huge phages likely use these genes to redirect the ribosomes to make more copies of their own proteins at the expense of bacterial proteins. Some huge phages also have alternative genetic codes, the nucleic acid triplets that code for a specific amino acid, which could confuse the bacterial ribosome that decodes RNA.

In addition, some of the newly discovered huge phages carry genes for variants of the Cas proteins found in a variety of bacterial CRISPR systems, such as the Cas9, Cas12, CasX and CasY families. CasØ is a variant of the Cas12 family. Some of the huge phages also have CRISPR arrays, which are areas of the bacterial genome where snippets of viral DNA are stored for future reference, allowing bacteria to recognize returning phages and to mobilize their Cas proteins to target and cut them up.

"The high-level conclusion is that phages with large genomes are quite prominent across Earth's ecosystems, they are not a peculiarity of one ecosystem," Banfield said. "And phages which have large genomes are related, which means that these are established lineages with a long history of large genome size. Having large genomes is one successful strategy for existence, and a strategy we know very little about."

The researchers divided the 351 megaphages into 10 new groups, or clades, named after words for "big" in the languages of the paper's co-authors: Mahaphage (Sanskrit), Kabirphage, Dakhmphage and Jabbarphage (Arabic); Kyodaiphage (Japanese); Biggiephage (Australian), Whopperphage (American); Judaphage (Chinese), Enormephage (French); and Kaempephage (Danish).

HOUSTON -- Loss of an important tumor-suppressing gene allows head and neck cancer to spin off signals to nearby nerves, changing their function and recruiting them to the tumor, where they fuel growth and cancer progression, researchers from The University of Texas MD Anderson Cancer Center report in the journal Nature today.

By cracking the mechanism that launches neuronal invasion of tumors, a known marker of poor prognosis for patients, the team has uncovered possible avenues to block the process, including the use of drugs commonly used to treat blood pressure and irregular heartbeat.

"Tons of studies show that patients who have lots of nerves in their tumor are doing worse - recurrence rates are higher, survival is shorter," says co-first author Moran Amit, M.D., Ph.D., assistant professor of Head and Neck Surgery. "Nerve endings found in surgically removed tumors can't be easily characterized or tracked back to their source, so it's been a neglected field, a neglected hallmark of cancer."

"When surgeons remove head and neck cancers and find a high degree of nerve invasion, post-surgical radiation sometimes is effective," said co-senior author Jeffrey Myers, M.D., Ph.D., chair of Head and Neck Surgery. "But we really haven't understood whether the tumor was growing into the nerves or the nerve growing into the tumor and what signaling drove those interactions."

Co-senior author George Calin, M.D., Ph.D., professor of Experimental Therapeutics and an expert on non-coding RNAs added that the paper "puts together for the first time the mechanism of involvement of neurons in tumor generation, a new hallmark of cancer."

The team found that the neurons that invade the tumor are adrenergic nerves, which are involved in stress response. These nerves' neurotransmitters - adrenaline (epinephrine) and noradrenaline (norepinephrine) - are susceptible to drugs known as alpha and beta blockers, long used to treat high blood pressure and irregular heartbeats.

In the study, mice with oral cancer treated with the adrenergic blocker carvedilol had sharply lower tumor growth and cancer cell proliferation. Myers says the team is working to develop clinical trials of adrenergic blockers, most likely in combination with other drugs.

"We used to think that nerves are just randomly growing into the tumor, and that's completely wrong," Amit says.

Loss of p53 flips a microRNA switch to re-program neurons

Damage to the p53 gene is a major characteristic of head and neck cancers. A tumor-suppressing master transcriptional gene that governs the expression of many other genes, p53 is also mutated in a variety of cancers.

The team found high density of neurons in p53-deficient mouse models and human xenograft tumors of oral cavity squamous cell carcinoma (OCSCC) as well as increased neural growth in clusters of nerves exposed to p53-deficient OCSCC.

The researchers also discovered that oral cancer communicates with nerves by launching extracellular vesicles - membrane balls that carry various molecules - packed with microRNAs to connect with the nerves. The miRNA cargo varied depending on p53 status of the tumors.

"When you have intact p53, you have specific types of microRNAs that keep neurons in a quiescent state," Amit says. "Once you lose p53, the micro RNA population within the exosomes changes and then you get positive signals to induce nerve growth."

Investigators identified adrenergic nerves extending into the tumors and suspected they were extensions of pre-existing nerves. However, when they cut adrenergic nerves before inducing tumors in mice, adrenergic nerves still appeared in the tumor and the tumors still grew.

Subsequent experiments showed the miRNAs in vesicles from p53-deficient tumors were connecting instead with existing sensory nerves, a different nerve type, and actually changing them into the adrenergic type. These neo-adrenergic nerves then invaded the tumor.

To confirm this finding, they cut sensory nerves ahead of inducing p53-deficient tumors in mice. Without the sensory nerve targets for the vesicles, the tumor shrank.

Impact of adrenergic nerve density on patients

To validate the impact of their findings on people with OCSCC, the researchers analyzed the presence of adrenergic nerves in the tumors of 70 patients who were treated at MD Anderson. Adrenergic nerve density in the tumors was associated with lower recurrence-free survival and overall survival.

The statistical significance of the adrenergic nerve densities held up in multivariable analysis after adjustment for other variables, such as age, sex, cancer stage, surgical margin status, overall neuronal invasion and treatment type. They suggest nerve density measurements merit exploration as a predictive marker of oral cancer aggressiveness. Myers, Calin, Amit and colleagues believe the paper opens up a new area for cancer researchers.

"Neurons control everything that we do in everyday life," Amit says. "They control our voluntary and involuntary bodily functions, so it's intuitive that they are involved in cancer."

A large proportion of highly active men watch more television than their low-active peers do. In contrast, highly active women watch less television than low-active women do.

revious studies have found prolonged television time to be more harmful to health than other domains of sedentariness. A recent longitudinal study with a ten-year follow-up examined how the television viewing time of Finnish adults was associated with their physical activity level during leisure-time.

The results showed that maintaining a high level of leisure-time physical activity was accompanied by less television viewing time for women. High television time (3 hours or more per day) especially was more prevalent among low-active women than it was among highly active women.

Surprisingly, highly active men tended to watch more television (approximately 2 hours per day) than did their low-active peers, who tended to watch television one hour or less a day. Highly active men seemed to have time for physical activity as well as television viewing.

The researchers thought about the reasons behind the differences between genders.

"One reason might be the different motivations men and women have for participating in physical activities," says Senior Researcher Xiaolin Yang from the LIKES Research Centre for Physical Activity and Health: "According to a previous study, men have more intrinsic orientation, meaning mastery and competition, whereas women have more extrinsic orientation, for example appearance and physical condition. Additionally, women are usually more health-conscious than men are. Thus, the health consciousness of physically active women may have an additive effect on their decision-making regarding television viewing as well."

Irinja Lounassalo, a PhD student at the Faculty of Sport and Health Sciences at the University of Jyväskylä, adds another point of view to the previous one: "The differences between genders may also be related to the use of leisure-time. According to time use studies, Finnish women spend nearly an hour more on household work on an average day than Finnish men do. Thus, those women devoting more time to physical activity might take the time for it from television time - not, for example, from housework."

Researchers at North Carolina State University have developed a new technique for shielding electronics in military and space exploration technology from ionizing radiation. The new approach is more cost effective than existing techniques, and the secret ingredient is...rust.

"Our approach can be used to maintain the same level of radiation shielding and reduce the weight by 30% or more, or you could maintain the same weight and improve shielding by 30% or more - compared to the most widely used shielding techniques," says Rob Hayes, co-author of a paper on the work and an associate professor of nuclear engineering at NC State. "Either way, our approach reduces the volume of space taken up by shielding."

Ionizing radiation can cause significant problems for electronic devices. To protect against this, devices that may be exposed to radiation - such as devices used in spacecraft - incorporate radiation shielding.

Weight is a significant factor in designing aerospace technologies, and the shielding most commonly found in aerospace devices consists of putting an aluminum box around any sensitive technologies. This has been viewed as providing the best tradeoff between a shield's weight and the protection it provides.

The new technique relies on mixing oxidized metal powder - rust - into a polymer, and then incorporating it into a common conformal coating on the relevant electronics.

"Metal oxide powder offers less shielding than metal powder would, but oxides are less toxic and don't pose electromagnetic challenges that could interfere with a device's operation," Hayes says.

"Radiation transport calculations show that inclusion of the metal oxide powder provides shielding comparable to a conventional shield," says Mike DeVanzo, a former graduate student at NC State and first author on the work. "At low energies, the metal oxide powder reduces both gamma radiation to the electronics by a factor of 300 and the neutron radiation damage by 225%."

"At the same time, the coating is less bulky than a shielding box," Hayes says. "And in computational simulations, the worst performance of the oxide coating still absorbed 30% more radiation than a conventional shield of the same weight.

"On top of that, the oxide particulate is much less expensive than the same amount of the pure metal," Hayes says.

"This could potentially reduce the need for conventional shielding materials on space-based electronics," adds DeVanzo, who works at Lockheed Martin Space.

The researchers are continuing to test and fine-tune their shielding technique for use in various applications.

"We're now looking for industry partners to help us develop the technology for commercial use," Hayes says.

By creating neatly spaced slits in a clay mineral, University of Groningen Professor of Experimental Solid State Physics Petra Rudolf was able to filter water to remove a toxic herbicide. After removing the pollutant by heating the material, the clay can be reused. Together with colleagues from Greece, Rudolf presents this proof of principle study in the journal Environmental Science Nano.

In the Netherlands, a lot of sugar beets are grown. On these fields, the herbicide chloridazon is widely used. This compound is toxic to humans, does not break down in nature and will eventually seep into the groundwater. Chloridazon concentrations in groundwater are currently below the safety threshold but as it is persistent in the environment, they are expected to increase. 'Water purification plants can break down chloridazon using UV light - but the breakdown products of chloridazon are also toxic,' explains Rudolf.

Pillars

Rudolf has acquired a technique to make well-defined nanocavities in clay, which she adapted to trap the herbicide. 'Clay is a layered mineral,' Rudolf explains. 'The layers have a negative charge and are separated by positive ions. We can replace those with molecular pillars of our own design.' The natural clays are first washed and then treated with sodium salts. The sodium replaces the natural positive ions between the layers. 'These sodium ions are surrounded by a water mantle, which pushes the layers slightly further apart. By simply adding the pillar molecules to the water, they will replace the sodium.'

These pillars are usually made of silicon oxide, with an added chemical group that defines the affinity of the cavities. Rudolf: 'In this case, we added copper ions to attract the chloridazon and its breakdown products.' The functionalized clay absorbed the herbicide in significant amounts: nearly 900 milligrams per kilogram of clay. 'This is a good result and we see scope to further increase the absorption.' Furthermore, Rudolf and her colleagues have shown that the herbicide is removed by heating the clay, which can then be used again.

Groundwater

The first results were obtained using 10 times the highest concentration of chloridazon measured in the environment. Furthermore, the experiments were performed in clean water. 'So, we need to repeat this in real groundwater, to see if other compounds affect the absorption.' If all these tests yield positive results, the next question is how to make this clay into a product that can be used in water treatment. 'The options are to add the clay to water and then retrieve it by filtration, or to build the clay into a membrane,' explains Rudolf.

By altering the width of the slits and changing the affinity of the pillars, different chemical compounds could be caught by the functionalized clay. 'We are testing systems to remove two other compounds from water,' says Rudolf. 'Furthermore, a similar system could be created using other layered materials, such as graphene oxide.'