Computers Math

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