Aurelia Butler

With a big assist from artificial intelligence and a heavy dose of human touch, Tim Cernak’s lab at the University of Michigan made a discovery that dramatically speeds up the time-consuming chemical process of building molecules that will be tomorrow’s medicines, agrichemicals or materials.
The discovery, published in the Feb. 3 issue of Science, is the culmination of years of chemical synthesis and data science research by the Cernak Lab in the College of Pharmacy and Department of Chemistry.
The goal of the research was to identify key reactions in the synthesis of a molecule, ultimately reducing the process to as few steps as possible. In the end, Cernak and his team achieved the synthesis of a complex alkaloid found in nature in just three steps. Previous syntheses took between seven and 26 steps.
“Making a chemical structure that has atoms in just the right place to give you efficacious and nontoxic medicines, for instance, is tricky,” said Cernak, assistant professor of medicinal chemistry and chemistry. “It requires a chemical synthesis strategy grounded in the chemical building blocks you can actually buy and then stitch together using chemical reactions.”
The accomplishment has powerful implications for speeding up the development of medicines.
Cernak compared the construction of these complex molecules to playing chess. You need to orchestrate a series of moves to get to the end of the game. While there’s a near infinite number of possible moves, there’s a logic that can be followed.
“We developed a logic here, based in graph theory, to get to the end as quickly as possible,” he said.
Cernak and colleagues used SYNTHIA Retrosynthesis Software, which provides scientists with a database of pathways, or steps, and formulas for millions of molecular structures. This gave the team an enormous amount of computational synthesis data to play with.
Using an algorithm they developed to curate the data, the researchers identified the steps along the pathway that were high impact, or key steps, and the steps that were making progress toward completing the synthesis but ultimately inefficient for the whole process.
“We hope this research can lead to better medicines,” Cernak said. “So far, we have been limited in the molecular structures we can quickly access with chemical synthesis.”
Co-authors include Yingfu Lin, senior research fellow in pharmacy; Rui (Sam) Zhang, doctoral student in chemistry; and Di Wang, doctoral student in pharmacy. More

An exciting prospect in modern optics is to exploit “patterns of light,” how the light looks in its many degrees of freedom, often referred to as structured light.
Each pattern could form an encoding alphabet for optical communication or might be used in manufacturing to enhance performance and productivity. Unfortunately, patterns of light get distorted when they pass through noisy channels, for instance, stressed optical fiber, aberrated optics, turbid living tissue, and perhaps a very severe example, atmospheric turbulence in air.
In all these examples, the distorted pattern can deteriorate to the point that the output pattern looks nothing like the input, negating the benefit. Now researchers from the University of the Witwatersrand (Wits University) in South Africa have shown how it is possible to find distortion-free forms of light that come out of a noisy channel exactly the same as they were put in.
Using atmospheric turbulence as an example, they showed that these special forms of light, called eigenmodes, can be found for even very complex channels, emerging undistorted, while other forms of structured light would be unrecognisable. Their research has been published in the journal, Advanced Photonics — the flagship journal of SPIE, the international society for optics and photonics.
“Passing light through the atmosphere is crucial in many applications, such as free-space optics, sensing and energy delivery, but finding how best to do this has proved challenging,” says Professor Andrew Forbes, head of the Structured Light Laboratory at Wits University.
Traditionally a trial-and-error approach has been used to find the most robust forms of light to some particular noisy channel, but to date all forms of familiar structured light have shown to be distorted as the medium become progressively more noisy. The reason is that we “see” the distortion.
To establish whether it is possible to create light that doesn’t “see” the distortion, passing through as if it wasn’t there the researchers treated the noisy channel as a mathematical operator and asked a simple question: “what forms of light would be invariant to this operator?.” In other words, what forms of light appear as the natural mode of the channel that it is in, so that it don’t see the distortion. This can also be called the true eigenmodes of the channel.
The example tackled was the severe case of distortions due to atmospheric turbulence. The answer to the problem revealed unrecognizable forms of light — in other words, light that is not in any well-known structured light family, but nevertheless completely robust to the medium. This fact was confirmed experimentally and theoretically for weak and strong turbulence conditions.
“What is exciting about the work is that it opens up a new approach to studying complex light in complex systems, for instance, in transporting classical and quantum light through optical fiber, underwater channels, living tissue and other highly aberrated systems,” says Forbes.
Because of the nature of eigenmodes, it doesn’t matter how long this medium is, nor how strong the perturbation, so that it should work well even in regimes where traditional corrective procedures, such as adaptive optics, fail.
“Maintaining the integrity of structured light in complex media will pave the way to future work in imaging and communicating through noisy channels, particularly relevant when the structured forms of light are fragile quantum states.” More

With cancer, diabetes and heart disease among the leading causes of disability and death in the United States, imagine a long-term, in-home monitoring solution that could detect these chronic diseases early and lead to timely interventions.
Zheng Yan and a team of researchers at the University of Missouri may have a solution. They have created an ultrasoft “skin-like” material — that’s both breathable and stretchable — for use in the development of an on-skin, wearable bioelectronic device capable of simultaneously tracking multiple vital signs such as blood pressure, electrical heart activity and skin hydration.
“Our overall goal is to help improve the long-term biocompatibility and the long-lasting accuracy of wearable bioelectronics through the innovation of this fundamental porous material which has many novel properties,” said Yan, an assistant professor in the Department of Chemical and Biomedical Engineering and the Department of Mechanical and Aerospace Engineering.
Made from a liquid-metal elastomer composite, the material’s key feature is its skin-like soft properties.
“It is ultrasoft and ultra-stretchable, so when the device is worn on the human body, it will be mechanically imperceptible to the user,” Yan said. “You cannot feel it, and you will likely forget about it. This is because people can feel about 20 kilopascals or more of pressure when something is stretched on their skin, and this material creates less pressure than that.”
Its integrated antibacterial and antiviral properties can also help prevent harmful pathogens from forming on the surface of the skin underneath the device during extended use.
“We call it a mechanical and electrical decoupling, so when the material is stretched, there is only a small change in the electrical performance during human motion, and the device can still record high-quality biological signals from the human body,” Yan said.
While other researchers have worked on similar designs for liquid-metal elastomer composites, Yan said the MU team has a novel approach because the breathable “porous” material they developed can prevent the liquid metal from leaking out when the material is stretched as the human body moves.
The work builds on the team’s existing proof of concept, as demonstrated by their previous work including a heart monitor currently under development. In the future, Yan hopes the biological data gathered by the device could be wirelessly transmitted to smartphone or similar electronics for future sharing with medical professionals.
“Porous liquid metal-elastomer composites with high leakage resistance and antimicrobial property for skin-interfaced bioelectronics” was published in Science Advances, a journal of the American Association for the Advancement of Science (AAAS). Co-authors on the study include Yadong Xu, Yajuan Su, Xianchen Xu, Brian Arends, Ganggang Zhao, Daniel Ackerman, Henry Huang, St. Patrick Reid, Joshua Santarpia, Chansong Kim, Zehua Chen, Sana Mahmoud, Yun Ling, Alexander Brown, Qian Chen, Guoliang Huang and Jingwei Xe.
This study was supported by grants from the National Science Foundation (2149721), Office of Naval Research (FA9550-21-1-0226), National Institute of General Medical Sciences (P30GM127200), National Institute of Arthritis and Musculoskeletal and Skin Diseases (R21AR080906), and the Air Force Office of Scientific Research (AF 9550-20-1-0279 and AFOSR FA9550-20-1-0257). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies. More

Researchers from the University of Sussex and Universal Quantum have demonstrated for the first time that quantum bits (qubits) can directly transfer between quantum computer microchips and demonstrated this with record-breaking speed and accuracy. This breakthrough resolves a major challenge in building quantum computers large and powerful enough to tackle complex problems that are of critical importance to society.
Today, quantum computers operate on the 100-qubit scale. Experts anticipate millions of qubits are required to solve important problems that are out of reach of today’s most powerful supercomputers [1, 2]. There is a global quantum race to develop quantum computers that can help in many important societal challenges from drug discovery to making fertilizer production more energy efficient and solving important problems in nearly every industry, ranging from aeronautics to the financial sector.
In the research paper, published today in Nature Communications, the scientists demonstrate how they have used a new and powerful technique, which they dub ‘UQ Connect’, to use electric field links to enable qubits to move from one quantum computing microchip module to another with unprecedented speed and precision. This allows chips to slot together like a jigsaw puzzle to make a more powerful quantum computer.
The University of Sussex and Universal Quantum team were successful in transporting the qubits with a 99.999993% success rate and a connection rate of 2424/s, both numbers are world records and orders of magnitude better than previous solutions.
Professor Winfried Hensinger, Professor of Quantum Technologies at the University of Sussex and Chief Scientist and Co-founder at Universal Quantum said: “As quantum computers grow, we will eventually be constrained by the size of the microchip, which limits the number of quantum bits such a chip can accommodate. As such, we knew a modular approach was key to make quantum computers powerful enough to solve step-changing industry problems. In demonstrating that we can connect two quantum computing chips — a bit like a jigsaw puzzle — and, crucially, that it works so well, we unlock the potential to scale-up by connecting hundreds or even thousands of quantum computing microchips.”
While linking the modules at world-record speed, the scientists also verified that the ‘strange’ quantum nature of the qubit remains untouched during transport, for example, that the qubit can be both 0 and 1 at the same time.

Dr Sebastian Weidt, CEO and Co-founder of Universal Quantum, and Senior Lecturer in Quantum Technologies at the University of Sussex said: “Our relentless focus is on providing people with a tool that will enable them to revolutionise their field of work. The Universal Quantum and University of Sussex teams have done something truly incredible here that will help make our vision a reality. These exciting results show the remarkable potential of Universal Quantum’s quantum computers to become powerful enough to unlock the many lifechanging applications of quantum computing.”
Universal Quantum has just been awarded €67 million from the German Aerospace Center (DLR) to build two quantum computers where they will deploy this technology as part of the contract. The University of Sussex spin-out was also recently named as one of the 2022 Institute of Physics award winners in the Business Start-up category.
Weidt added: “The DLR contract was likely one of the largest government quantum computing contracts ever handed out to a single company. This is a huge validation of our technology. Universal Quantum is now working hard to deploy this technology in our upcoming commercial machines.”
Dr Mariam Akhtar led the research during her time as Research Fellow at the University of Sussex and Quantum Advisor at Universal Quantum. She said: “The team has demonstrated fast and coherent ion transfer using quantum matter links. This experiment validates the unique architecture that Universal Quantum has been developing — providing an exciting route towards truly large-scale quantum computing.”
Professor Sasha Roseneil, Vice-Chancellor of the University of Sussex, said: “It’s fantastic to see that the inspired work of the University of Sussex and Universal Quantum physicists has resulted in this phenomenal breakthrough, taking us a significant step closer to a quantum computer that will be of real societal use. These computers are set to have boundless applications — from improving the development of medicines, creating new materials, to maybe even unlocking solutions to the climate crisis. The University of Sussex is investing significantly in quantum computing to support our bold ambition to host the world’s most powerful quantum computers and create change that has the potential to positively impact so many people across the world. And with teams spanning the spectrum of quantum computing and technology research, the University of Sussex has both a breadth and a depth of expertise in this. We are still growing our research and teaching in this area, with plans for new teaching programmes, and new appointments.”
Professor Keith Jones, Interim Provost and Pro-Vice Chancellor for Research and Enterprise at the University of Sussex, said of the development: “This is a very exciting finding from our University of Sussex physicists and Universal Quantum. It proves the value and dynamism of this University of Sussex spin-out company, whose work is grounded in rigorous and world-leading academic research. Quantum computers will be pivotal in helping to solve some of the most pressing global issues. We’re delighted that Sussex academics are delivering research that offers hope in realising the positive potential of next-generation quantum technology in crucial areas such as sustainability, drug development, and cybersecurity.”
NOTES
[1] Webber, M., et. al. AVS Quantum Sci. 4, 013801 (2022)
[2] Lekitsch, B., et al., Science Advances, 3(2), 1-12 (2017) More

How do you build complex structures for housing cells using a material as soft as jelly? Rice University scientists have the answer, and it represents a potential leap forward for regenerative medicine and medical research in general.
Researchers in the lab of Rice’s Jeffrey Hartgerink have figured out how to 3D-print the well-defined structures using a self-assembling peptide ink. “Eventually, the goal is to print structures with cells and grow mature tissue in a petri dish. These tissues can then be transplanted to treat injuries, or used to learn about how an illness works and to test drug candidates,” said Adam Farsheed, a Rice bioengineering graduate student and lead author of the study, which appeared in Advanced Materials.
“There are 20 naturally occurring amino acids that make up proteins in the human body,” Farsheed said. “Amino acids can be linked together into larger chains, like Lego blocks. When amino acid chains are longer than 50 amino acids, they are called proteins, but when these chains are shorter than 50 amino acids they are called peptides. In this work, we used peptides as our base material in our 3D-printing inks.”
Developed by Hartgerink and collaborators, these “multidomain peptides” are designed to be hydrophobic on one side and hydrophilic on the other. When placed in water, “one of the molecules will flip itself on top of another, creating what we call a hydrophobic sandwich,” Farsheed said.
These sandwiches stack onto one another and form long fibers, which then form a hydrogel, a water-based material with a gelatinous texture that can be useful for a wide range of applications such as tissue engineering, soft robotics and wastewater treatment.
Multidomain peptides have been used for nerve regeneration, cancer treatment and wound healing, and have been shown to promote high levels of cell infiltration and tissue development when implanted in living organisms.

“We know that the multidomain peptides can safely be implanted in the body,” Farsheed said. “But what I was looking to do in this project was to go in a different direction and show that these peptides are a great 3D-printing ink.
“It might be counterintuitive since our material is so soft, but I recognized that our multidomain peptides are an ideal ink candidate because of the way they self-assemble,” he continued. “Our material can reassemble after being deformed, similar to how toothpaste forms a nice fiber when pushed out of a tube.”
Farsheed’s mechanical engineering background allowed him to take an unconventional approach when testing his hypothesis.
“I had more of a brute-force engineering approach where instead of chemically modifying the material to make it more amenable to 3D printing, I tested to see what would happen if I simply added more material,” he said. “I increased the concentration about fourfold, and it worked extremely well.
“There have been only a handful of attempts to 3D-print using other self-assembling peptides, and that work is all great, but this is the first time that any self-assembling peptide system has been used to successfully 3D-print such complex structures,” Farsheed continued.
The structures were printed with either positively charged or negatively charged multidomain peptides, and immature muscle cells placed on the structures behaved differently depending on the charge. Cells remained balled up on the substrate with a negative charge, while on the positively charged material the cells spread out and began to mature.
“It shows that we can control cell behavior using both structural and chemical complexity,” Farsheed said.
Hartgerink is a professor of chemistry and bioengineering and associate chair for undergraduate studies. Farsheed is a bioengineering graduate student and lead author on the study. Additional study co-authors are undergraduate student Adam Thomas and graduate student Brett Pogostin.
The National Institutes of Health (R01 DE021798) and the National Science Foundation Graduate Research Fellowships Program supported the research. More

A synthetic biosensor that mimics properties found in cell membranes and provides an electronic readout of activity could lead to a better understanding of cell biology, development of new drugs, and the creation of sensory organs on a chip capable of detecting chemicals, similar to how noses and tongues work.
A study, “Cell-Free Synthesis Goes Electric: Dual Optical and Electronic Biosensor vie Direct Channel Integration into a Supported Membrane Electrode,” was published Jan. 18 in the Synthetic Biology journal of the American Chemical Society.
The bioengineering feat described in the paper uses synthetic biology to re-create a cell membrane and its embedded proteins, which are gatekeepers of cellular functions. A conducting sensing platform allows for an electronic readout when a protein is activated. Being able to test if and how a molecule reacts with proteins in a cell membrane could generate a great many applications.
But embedding membrane proteins into sensors had been notoriously difficult until the study’s authors combined bioelectronic sensors with a new approach to synthesize proteins.
“This technology really allows us to study these proteins in ways that would be incredibly challenging, if not impossible, with current technology,” said first author Zachary Manzer, a doctoral student in the lab of senior author Susan Daniel, the Fred H. Rhodes Professor and director of the Robert Frederick Smith School of Chemical and Biomolecular Engineering at Cornell Engineering.
Proteins within cell membranes serve many important functions, including communicating with the environment, catalyzing chemical reactions, and moving compounds and ions across the membranes. When a membrane protein receptor is activated, charged ions move across a membrane channel, triggering a function in the cell. For example, brain neurons or muscle cells fire when cues from nerves signal charged calcium-ion channels to open.

The researchers have created a biosensor that starts with a conducting polymer, which is soft and easy to work with, on top of a support that together act as an electric circuit that is monitored by a computer. A layer of lipid (fat) molecules, which forms the membrane, lies on top of the polymer, and the proteins of interest are placed within the lipids.
In this proof of concept, the researchers have created a cell-free platform that allowed them to synthesize a model protein directly into this artificial membrane. The system has a dual readout technology built in. Since the components of the sensor are transparent, researchers can use optical techniques, such as engineering proteins that fluoresce when activated, which allows scientists to study the fundamentals via microscope, and observe what happens to the protein itself during a cellular process. They can also record electronic activity to see how the protein is functioning through clever circuit design.
“This really is the first demonstration of leveraging cell-free synthesis of transmembrane proteins into biosensors,” Daniel said. “There’s no reason why we wouldn’t be able to express many different kinds of proteins into this general platform.”
Currently, researchers have used proteins grown and extracted from living cells for similar applications, but given this advance, users won’t have to grow proteins in cells and then harvest and embed them in the membrane platform. Instead, they can synthesize them directly from DNA, the basic template for proteins.
“We can bypass the whole process of the cell as the factory that produces the protein,” Daniel said, “and biomanufacture the proteins ourselves.”
With such a system, a drug chemist interested in a particular protein implicated in a disease might flow potentially therapeutic molecules across that protein to see how it responds. Or a scientist looking to create an environmental sensor could place on the platform a particular protein that is sensitive to a chemical or pollutant, such as those found in lake water.

“If you think of your nose, or your tongue, every time you smell or taste something, ion channels are firing,” Manzer said. Scientists may now take the proteins being activated when we smell something and translate the results into this electronic system to sense things that might be undetectable with a chemical sensor.”
The new sensor opens the door for pharmacologists to research how to create non-opioid pain medicines, or drugs to treat Alzheimer’s or Parkinson’s disease, which interact with cell membrane proteins.
Surajit Ghosh, a postdoctoral researcher in Daniel’s lab, is a co-first author. Neha Kamat, assistant professor of biomedical engineering at Northwestern University, is a senior co-author of the paper.
The study was funded by the National Science Foundation, the Air Force Office of Scientific Research, the American Heart Association, the National Institute of General Medical Sciences and the Defense Advanced Research Projects Agency. More

Parents: It might be time to rethink your family’s video-gaming rules.
New research findings challenge the fears parents have been hearing for years that children who spend hour after hour playing video games, or choose games of certain genres, would manifest unhealthy results in their cognitive ability.
“Our studies turned up no such links, regardless of how long the children played and what types of games they chose,” said Jie Zhang, associate professor of curriculum and instruction at the University of Houston College of Education and a member of the research team. The work is published in the Journal of Media Psychology.
In reaching the conclusions, researchers examined the video gaming habits of 160 diverse urban public-school preteen students (70% from lower income households), which represents an age group less studied in previous research. Participating students reported playing video games an average of 2.5 hours daily, with the group’s heaviest gamers putting in as much as 4.5 hours each day.
The team looked for association between the students’ video game play and their performance on the standardized Cognitive Ability Test 7, known as CogAT, which evaluates verbal, quantitative and nonverbal/spatial skills. CogAT was chosen as a standard measure, in contrast to the teacher-reported grades or self-reported learning assessments that previous research projects have relied on.
“Overall, neither duration of play nor choice of video game genres had significant correlations with the CogAT measures. That result shows no direct linkage between video game playing and cognitive performance, despite what had been assumed,” said May Jadalla, professor in the School of Teaching and Learning at Illinois State University and the study’s principal investigator.
But the study revealed another side of the issue, too. Certain types of games described as helping children build healthy cognitive skills also presented no measurable effects, in spite of the games’ marketing messages.
“The current study found results that are consistent with previous research showing that types of gameplay that seem to augment cognitive functions in young adults don’t have the same impact in much younger children,” said C. Shawn Green, professor in the Department of Psychology at the University of Wisconsin-Madison.
Does this mean the world can play on? Maybe, the research suggests. But the experts also caution that gaming time took the heaviest players’ away from other, more productive activities — homework, to be specific — in a process psychologists call displacement. But even in those cases, the differences were slight between those participants and their peers’ CogAT measures of cognitive abilities.
“The study results show parents probably don’t have to worry so much about cognitive setbacks among video game-loving children, up to fifth grade. Reasonable amounts of video gaming should be OK, which will be delightful news for the kids. Just keep an eye out for obsessive behavior,” said Zhang. “When it comes to video games, finding common ground between parents and young kids is tricky enough. At least now we understand that finding balance in childhood development is the key, and there’s no need for us to over-worry about video gaming.”
The study was funded by the National Science Foundation. More