It’s possible that I shall make an ass of myself. But in that case one can always get out of it with a little dialectic. I have, of course, so worded my proposition as to be right either way (K.Marx, Letter to F.Engels on the Indian Mutiny)
Thursday, February 20, 2025
A new approach for breaking plastic waste down to monomers
Summary author: Meagan Phelan
American Association for the Advancement of Science (AAAS)
Researchers have reported a method for breaking down commercial polymers like Plexiglass into monomers, a form more desirable for reuse. This could help alleviate the growing plastic waste stream. Most current plastic recycling methods rely on macroscopic mechanical shredding, cleaning and reprocessing. As a result, the properties degrade relative to the virgin polymer. Chemical decomposition to the original monomer would enable more thorough purification and then repolymerization to restore ideal performance. Here, Hyun Suk Wang and colleagues report the discovery that in dichlorobenzene solvent, violet light irradiation can cleanly break down polymethacrylates such as Plexiglass to their original monomers. The process appears to involve hydrogen abstraction from the backbone by small quantities of chlorine radicals liberated from the solvent. “The possibility to perform multigram-scale depolymerizations and confer temporal control renders this methodology a versatile and general route to recycling,” say the authors.
Scientists have discovered a potentially greener way to produce a crucial industrial chemical used to make many everyday products from plastics and textiles to antifreeze and disinfectants, according to a new study published in Science and co-authored by Tulane University chemical engineer Matthew Montemore.
The breakthrough could significantly reduce greenhouse gas emissions from the manufacture of ethylene oxide, which has an estimated $40 billion global market. The current production process requires chlorine, which is toxic and emits millions of tons of carbon dioxide into the atmosphere annually.
The research team, led by Montemore, as well as Tufts University chemistry professor Charles Sykes and University of California Santa Barbara (UCSB) chemical engineering professor Phillip Christopher, found that adding small amounts of nickel atoms to silver catalysts can maintain production efficiency while eliminating the need for chlorine in the process.
“If industry does try this out and they find it to be useful and are able to commercialize it, the twin benefits are you can save a lot of CO2 and a lot of money at the same time,” Montemore said.
Getting rid of toxic chlorine could also make production safer, Montemore added.
The discovery was six years in the making. Sykes and Montemore first discussed exploring selective oxidation reactions in 2018. They focused on ethylene oxide production, which converts ethylene and molecular oxygen using silver as the primary catalyst.
"We were surprised because we couldn't find anything in the scientific or patent literature about nickel despite it being a common and inexpensive element used in many other catalytic processes," Sykes said.
The breakthrough came through applying Sykes' single-atom alloy concept, a fundamental approach to understanding and controlling chemical reactions that he pioneered over a decade ago. Montemore thought this approach could be applied to oxidation reactions, even though Sykes had not had much success with oxidation in the past.
Montemore performed calculations to screen for promising combinations of metals. Based on these calculations, PhD students Elizabeth Happel and Laura Cramer at Tufts conducted initial experiments that showed promising results.
The team then enlisted Christopher, an expert on catalytic reactor studies, to develop a practical formulation of the silver catalyst with nickel additions.
The results exceeded expectations.
Anika Jalil, a doctoral student at UCSB successfully developed a reproducible method for incorporating nickel atoms into the silver catalyst, a technical challenge that may explain why this effect had never been previously reported.
The current industrial process for producing ethylene oxide typically generates two molecules of carbon dioxide per ethylene oxide molecule. Adding chlorine improves this ratio to about two molecules of ethylene oxide per carbon dioxide molecule. The new nickel-enhanced catalyst could potentially reduce these emissions further while eliminating the need for toxic chlorine in the process.
The team has submitted international patents for their discovery and is in discussions with a major commercial producer about implementing the technology in existing manufacturing facilities.
If successful, this cleaner production method could help address the significant environmental impact of ethylene oxide manufacturing while maintaining the efficiency needed for industrial-scale production.
Nickel promotes selective ethylene epoxidation on silver
Article Publication Date
20-Feb-2025
S D G: SUSTAINABLE DEVELOPMENT GOALS
3D lung model raises the bar for research
Adaptable model can replicate realistic breathing maneuvers and offer personalized evaluation of aerosol therapeutics under various breathing conditions
University of Delaware Assistant Professor Catherine Fromen and current graduate student Dominic Hoffman work with an adaptable lung model that can replicate realistic breathing maneuvers and offer personalized evaluation of aerosol therapeutics under various combinations of breathing conditions, formulations and parameters. They are testing to see the effectiveness of inhalable medications in the model.
Credit: Kathy F. Atkinson / University of Delaware
Respiratory diseases are a challenging problem to treat. Inhalable medicines are a promising solution that depend on the ability to deliver tiny particles known as aerosols to the correct location in the lungs at the correct dosage.
How effectively this works can get complicated, depending on the drug, delivery method and patient. This is because it is difficult to predict just how much medicine gets in and where it goes in the lung. Similar challenges exist when thinking about measuring an inhaled environmental exposure, say to particles of asbestos or a toxin like smoke.
“If it's something environmental and toxic that we're worried about, knowing how far and how deep in the lung it goes is important,” said Catherine Fromen, University of Delaware Centennial Associate Professor for Excellence in Research and Education in the Department of Chemical and Biomolecular Engineering. “If it's designing a better pharmaceutical drug for asthma or a respiratory disease, knowing exactly where the inhaled aerosol lands and how deep the medicine can penetrate will predict how well that works.”
Fromen and two UD alumni have developed an adaptable 3D lung model that can replicate realistic breathing maneuvers and offer personalized evaluation of aerosol therapeutics under various breathing conditions. The researchers have submitted a patent application on the invention through UD’s Office of Economic Innovation and Partnerships (OEIP), the unit responsible for managing intellectual property at UD.
In a paper published in the journal Device, Fromen and her team demonstrate how their new 3D lung model can advance understanding of how inhalable medications behave in the upper airways and deeper areas of the lung. This can provide a broader picture on how to predict the effectiveness of inhalable medications in models and computer simulations for different people or age groups. The researchers detail in the paper how they built the 3D structure and what they’ve learned so far.
Valuable research tool
The purpose of the lung is gas exchange. In practice, the lung is often approximated as the size of a tennis court that is exchanging oxygen and carbon dioxide with the bloodstream in our bodies. This is a huge surface area, and that function is critical — if your lungs go down, you're in trouble.
Fromen described this branching lung architecture like a tree that starts with a trunk and branches out into smaller and smaller limbs, ranging in size from a few centimeters in the trachea to about 100 microns (roughly the combined width of two hairs on your head) in the lung’s farthest regions. These branches create a complex network that filters aerosols as they travel through the lung. Just as tree branches end in leaves, the lung’s branches culminate in delicate, leaf-like structures called alveoli, where gases are exchanged.
“Those alveoli in the deeper airways make the surface area that provides this necessary gas exchange, so you don't want environmental things getting in there where they can damage these sensitive, finer structures,” said Fromen, who has a joint appointment in biomedical engineering.
Mimicking the complex structure and function of the lung in a lab setting is inherently challenging. The UD-developed 3D lung model is unique in several ways. First, the model breathes in the same cyclic motion as an actual lung. That’s key, Fromen said. The model also contains lattice structures to represent the entire volume and surface area of a lung. These lattices, made possible through 3D printing, are a critical innovation, enabling precise design to mimic the lung's filtering processes without needing to recreate its full biological complexity.
“There's nothing currently out there that has both of these features,” she explained. “This means that we can look at the entire dosage of an inhaled medicine. We can look at exposure over time, and we can capture what happens when you inhale the medication and where the medicine deposits, as well as what gets exhaled as you breathe.”
The testing process
Testing how far an aerosol or environmental particle travels inside the 3D lung model is a multi-step process. The exposure of the model to the aerosol only takes about five minutes, but the analysis is time-consuming. The researchers add fluorescent molecules to the solution being tested to track where the particles deposit inside the model’s 150 different parts.
“We wash each part and rinse away everything that deposits. The fluorescence is just a molecule in the solution. When it deposits, we know the concentration of that, so, when we rinse it out, we can measure how much fluorescence was recovered,” Fromen said.
This data allows them to create a heat map of where the aerosols deposit throughout the lung model’s airways, which then can be validated against benchmarked clinical data for where such aerosols would be expected to go in a human under similar conditions.
The team’s current model matches a healthy person under sitting/breathing conditions for a single aerosol size, but Fromen’s team is working to ensure the model is versatile across a much broader range of conditions.
“An asthma attack, exercise, cystic fibrosis, chronic obstructive pulmonary disorder (COPD) — all those things are going to really affect where aerosols deposit. We want to make sure our model can capture those differences,” Fromen said.
The ability to look at specific disease features, say, narrowing of the airways or accumulation of mucus, could one day contribute to more personalized care. For example, perhaps a patient might need longer doses of medicine because the medication is not getting saturated in the body site, or possibly they need a redesigned patient inhaler, so it targets a specific region. This is currently difficult to implement, but the UD-developed model provides a baseline tool for asking those questions.
“This is important because, right now, inhaled pharmaceutics are designed with a one-size-fits-all approach. But someone who has severe COPD, for example, is going to breathe very differently and have a very different lung structure than someone who is healthy,” Fromen said.
Additionally, many inhaled medicines fail clinical trials for unknown reasons. When it doesn't work, researchers wonder, is it the molecule that isn’t effective, was the formulation flawed? Or did the molecule fail to accumulate at a certain level at its target in the lungs?
According to Fromen, clinical trials typically focus on whether a medication results in measurable improvement in a disease, while the UD-developed tool can provide deeper insights. It can determine whether the aerosol got where it needed to go in the first place, and in the right amount, potentially saving time and effort in formulation development and reducing setbacks during clinical trials.
The researchers shared their design and methods in an open-source format, in hopes others will adopt the UD-developed technique.
“Making it accessible to other researchers opens the door for impactful collaborations,” Fromen said. “Clinicians can provide priority patient profiles for us to model, while pharmaceutical developers could integrate the model into their workflows to optimize treatments for specific respiratory conditions.”
Beyond applications in pharmaceutical development, the UD-developed model is also proving valuable in other fields. In a newly funded project with the Army Research Lab, in partnership with a group at Aberdeen Proving Ground, Fromen is using the UD-developed model to help toxicology researchers understand environmental exposures — not only how far things get in, but how much gets in over a given time span and how much is depositing in what regions of the lung, and what the impact is, positive or negative.
When even the most highly trained surgeons perform procedures on the retina—one of the smallest, most delicate parts of the human body—the stakes are high. Surgeons must account for patients’ breathing, snoring, and eye movements, along with their own involuntary hand tremors, while they work on a layer of cells less than a millimeter thick.
That’s why researchers at the University of Utah’s John A. Moran Eye Center and the John and Marcia Price College of Engineering have collaborated to create a new robotic surgery device that aims to give surgeons “superhuman” hands.
The robot itself is extremely precise, executing movements as small as one micrometer (smaller than a single human cell). It is mounted directly to the patient’s head using a helmet, such that subtle (and sometimes not so subtle) movements of the patient’s head are compensated for, keeping the eye quite still from the perspective of the robot. The robot also scales down the surgeon’s movements, measured using a handheld robotic device known as a haptic interface, to the much smaller surgical site within the eye, compensating for hand tremors along the way.
While still in the testing stages, the device aims to improve outcomes for patients and support cutting-edge procedures, including the delivery of gene therapies for inherited retinal diseases.
The researchers successfully tested the robot using enucleated pig eyes, publishing their results this week in the journal Science Robotics. The study was led by Jake Abbott, a professor in the U’s Department of Mechanical Engineering, and Moran Eye Center retinal specialist Paul S. Bernstein.
The retina is home to the light-sensitive rod and cone cells that form the basis of vision. Several inherited disorders cause those cells to form incorrectly, leading to vision impairments of varying severity, but new gene therapy techniques could reverse those conditions.
“Treatments for vision disorders are rapidly advancing,” Abbott said. “We need to give surgeons better ability to keep up with them.”
The first gene therapy approved by the U.S. Food and Drug Administration for an inherited retinal disease, for example, requires an injection into the space between the retina and another layer of cells known as the retinal pigment epithelium. In addition to the complications presented by eye movement and hand tremors, this subretinal target is vanishingly small; the surgeon must introduce the drug between two submillimeter-thin cell layers.
Because the device is not yet approved to operate on human subjects, testing required a human volunteer fitted with special goggles that allowed an animal eye to be mounted just in front of their natural eye. This allowed the researchers to test the robot’s ability to compensate for head motion and correct for hand tremors, all while operating on animal tissue, at no risk to the volunteer.
In the experiments described in the study, the surgeons achieved higher success rates while using the surgical robot device to perform subretinal injections while also avoiding ophthalmic complications.
These results demonstrate the robot has the potential to improve patient care, according to co-author Eileen Hwang, a Moran Eye Center retinal surgeon.
“The unique feature of this robot, head mounting, may make it possible for patients to have subretinal injections under intravenous (IV) sedation, rather than general anesthesia,” Hwang said. “IV sedation allows for faster recovery and is safer in some patients. Robots may also allow for more precise delivery of gene therapy medication compared to manual injections for more reproducible, safer treatments.”
As the robot makes its way from the lab to the operating room, its journey will be bolstered by the kind of interdisciplinary collaborations that first brought it to life.
“These collaborations are just wonderful at the University of Utah,” Bernstein said. “When I have ideas, the engineers, the chemists, the physics, are just a few blocks away.”
These results were published under the title, “Head-mounted Robots are an Enabling Technology for Subretinal Injections,” online Feb. 19 in the journal Science Robotics.
Co-authors include Abbott lab members Nicholas Posselli and Zachary Olson and Aaron Nagiel of the University of Southern California’s Keck School of Medicine. The research was supported by the National Eye Institute of the National Institutes of Health; Research to Prevent Blindness; the Las Madrinas Endowment in Experimental Therapeutics for Ophthalmology; and a Knights Templar Eye Foundation Endowment.
Journal
Science Robotics
Method of Research
Experimental study
Subject of Research
Animal tissue samples
Article Title
Head-mounted surgical robots are an enabling technology for subretinal injections
Article Publication Date
19-Feb-2025
COI Statement
A.N. is a consultant for Eyebiotech, Ultragenyx, Blackstone, Immuneering, Lexitas, Astellas, and Janssen. All other authors declare that they have no competing interests
New Ebola virus research boosts pandemic preparedness
Promising antibody may prove useful against deadly outbreaks
The model on the left shows how the Ebola virus stalk has a compact conformation, which blocks the site where mAb 3A6 would bind. The model on the right shows how this portion of the stalk can adopt an extended, or lifted, conformation, which would allow mAb 3A6 to access its binding domain.
Credit: Saphire Lab, published in Nature Communications, January 2025.
LA JOLLA, CA—New research led by scientists at La Jolla Institute for Immunology (LJI) reveals the workings of a human antibody called mAb 3A6, which may prove to be an important component for Ebola virus therapeutics.
This antibody was isolated from blood samples from an Ebola survivor treated at Emory University Hospital during the 2014-2016 Ebola virus outbreak, an outbreak that began in West Africa and killed more than 11,300 people.
In their new study, the researchers showed that mAb 3A6 helps block infection by binding to an important part of Ebola's viral structure, called the "stalk." Study collaborators at the NIH's National Institute of Allergy and Infectious Diseases (NIAID) found that treatment with mAb 3A6 can benefit non-human primates in advanced stages of Ebola virus disease.
"This antibody offers the best protection in primates, at the lowest dose yet seen for any single antibody," says LJI Professor, President & CEO Erica Ollmann Saphire, Ph.D., MBA, who led the recent Nature Communications study alongside John A. G. Briggs, Ph.D., of Cambridge University and the Max Planck Institute of Biochemistry; Gabriella Worwa, D.V.M., and Jens H. Kuhn, M.D., Ph.D., of NIAID; and Carl W. Davis, Ph.D., and Rafi Ahmed, Ph.D., of the Emory Vaccine Center.
The discovery that mAb 3A6 appears effective at a very low dose is also exciting. "The lower the amount of an antibody you can deliver to someone, the easier it will be to manufacture a treatment—and the lower the cost," says study first author Kathryn Hastie, Ph.D., LJI Instructor and Director of LJI's Center for Antibody Discovery.
How the antibody works
The key to treating Ebola virus is to find antibodies that anchor tightly to and block essential machinery of the virus. The researchers zeroed in on mAb 3A6 because it appears to target a structure on Ebola virus called the "stalk." The stalk is an important part of the Ebola virus structure because it anchors Ebola's glycoprotein structure (which drives entry into a host cell) to Ebola's viral membrane.
The team spearheaded efforts to capture images of mAb 3A6 in action. The researchers used two imaging techniques, called cryoelectron tomography and x-ray crystallography, to show how mAb 3A6 binds to Ebola virus to interrupt the infection process.
The researchers found that mAb 3A6 binds to a site normally concealed by a shifting landscape of viral proteins. "There's a dynamic movement in these proteins," says Hastie. "They might kind of wiggle around, move back and forth, maybe lean over a little bit or go up and down."
Antibody mAb 3A6 takes advantage of this little protein dance. It has such a strong affinity for its viral target that it can slip between the proteins, lift them up, and latch on its target.
Hastie says mAb 3A6's ability to bind to this target is important for several reasons. First, the site is conserved across different species of Ebola virus, making antibodies that target this region an attractive component in "pan-Ebolavirus" therapeutics. Second, the new understanding of how mAb 3A6 "lifts up" proteins in the viral stalk gives scientists a clearer view of Ebola's weaknesses. MAb 3A6 also shows us how similar antibodies against the stalks of other viruses might work as well.
"This study gives us some hints for how to design vaccines that are specifically against this region of Ebola virus," says Hastie.
Additional authors of the study, "Anti-Ebola virus mAb 3A6 protects highly viremic animals from fatal outcome via binding GP(1,2) in a position elevated from the virion membrane," include Zhe “Jen” Li Salie, who solved the X-ray structure; Zunlong Ke, who performed the cryoelectron tomography; Lisa Evans DeWald, Sara McArdle, Ariadna Grinyó, Edgar Davidson, Sharon L. Schendel, Chitra Hariharan, Michael J. Norris, Xiaoying Yu, Chakravarthy Chennareddy, Xiaoli Xiong, Megan Heinrich, Michael R. Holbrook, Benjamin Doranz, Ian Crozier, Yoshihiro Kawaoka, Luis M. Branco, Jens H. Kuhn
This study was supported in part by the National Institute of Health's National Institute for Allergy and Infectious Diseases (grant U19 AI142790, Contract No. HHSN272201400058C, Contract No. HHSN272200700016I, Contract No. HHSN272201800013C), DARPA (contract W31P4Q-14-1-0010), and UK Medical Research Council (grant MC_UP_1201/16), the European Research Council (ERC-CoG-648432 MEMBRANEFUSION), and the Max Planck Society.
Anti-Ebola virus mAb 3A6 protects highly viremic animals from fatal outcome via binding GP(1,2) in a position elevated from the virion membrane
Article Publication Date
17-Feb-2025
COI Statement
A.G., E.D., and B.J.D. are employees of Integral Molecular, and B.J.D. is a shareholder in that company. The remaining authors declare no competing interests.
