Computers Math

A strategy for cellular reprogramming involves using targeted genetic interventions to engineer a cell into a new state. The technique holds great promise in immunotherapy, for instance, where researchers could reprogram a patient’s T-cells so they are more potent cancer killers. Someday, the approach could also help identify life-saving cancer treatments or regenerative therapies that repair disease-ravaged organs.
But the human body has about 20,000 genes, and a genetic perturbation could be on a combination of genes or on any of the over 1,000 transcription factors that regulate the genes. Because the search space is vast and genetic experiments are costly, scientists often struggle to find the ideal perturbation for their particular application.
Researchers from MIT and Harvard University developed a new, computational approach that can efficiently identify optimal genetic perturbations based on a much smaller number of experiments than traditional methods.
Their algorithmic technique leverages the cause-and-effect relationship between factors in a complex system, such as genome regulation, to prioritize the best intervention in each round of sequential experiments.
The researchers conducted a rigorous theoretical analysis to determine that their technique did, indeed, identify optimal interventions. With that theoretical framework in place, they applied the algorithms to real biological data designed to mimic a cellular reprogramming experiment. Their algorithms were the most efficient and effective.
“Too often, large-scale experiments are designed empirically. A careful causal framework for sequential experimentation may allow identifying optimal interventions with fewer trials, thereby reducing experimental costs,” says co-senior author Caroline Uhler, a professor in the Department of Electrical Engineering and Computer Science (EECS) who is also co-director of the Eric and Wendy Schmidt Center at the Broad Institute of MIT and Harvard, and a researcher at MIT’s Laboratory for Information and Decision Systems (LIDS) and Institute for Data, Systems and Society (IDSS).
Joining Uhler on the paper, which appears today in Nature Machine Intelligence, are lead author Jiaqi Zhang, a graduate student and Eric and Wendy Schmidt Center Fellow; co-senior author Themistoklis P. Sapsis, professor of mechanical and ocean engineering at MIT and a member of IDSS; and others at Harvard and MIT. More

Increased government investment in climate change mitigation is prompting agricultural sectors to find reliable methods for measuring their contribution to climate change. With that in mind, a team led by scientists at the University of Illinois Urbana-Champaign proposed a supercomputing solution to help measure individual farm field-level greenhouse gas emissions.
Although locally tested in the Midwest, the new approach can be scaled up to national and global levels and help the industry grasp the best practices for reducing emissions.
The new study, directed by natural resources and environmental sciences professor Kaiyu Guan, synthesized more than 25 of the group’s previous studies to quantify greenhouse gas emissions produced by U.S. farmland. The findings — completed in collaboration with partners from the University of Minnesota, Lawrence Berkeley National Laboratory and Project Drawdown, a climate solutions nonprofit organization — are published in the journal Earth Science Reviews.
“There are many farming practices that can go a long way to reduce greenhouse gas emissions, but the scientific community has struggled to find a consistent method for measuring how well these practices work,” Guan said.
Guan’s team built a solution based on “agricultural carbon outcomes,” which it defines as the related changes in greenhouse gas emissions from farmers adopting climate mitigation practices like cover cropping, precision nitrogen fertilizer management and use of controlled drainage techniques.
“We developed what we call a ‘system of systems’ solution, which means we integrated a variety of sensing techniques and combined them with advanced ecosystem models,” said Bin Peng, co-author of the study and a senior research scientist at the U. of I. Institute for Sustainability, Energy and Environment. “For example, we fuse ground-based imaging with satellite imagery and process that data with algorithms to generate information about crop emissions before and after farmers adopt various mitigation practices.”
“Artificial intelligence also plays a critical role in realizing our ambitious goals to quantify every field’s carbon emission,” said Zhenong Jin, a professor at the University of Minnesota who co-led the study. “Unlike traditional model-data fusion approaches, we used knowledge-guided machine learning, which is a new way to bring together the power of sensing data, domain knowledge and artificial intelligence techniques.”
The study also details how emissions and agricultural practices data can be cross-checked against economic, policy and carbon market data to find best-practice and realistic greenhouse gas mitigation solutions locally to globally — especially in economies struggling to farm in an environmentally conscious manner. More

In a remarkable breakthrough in the field of Mathematical Science, Professor Kyudong Choi from the Department of Mathematical Sciences at UNIST has provided an irrefutable proof that certain spherical vortices exist in a stable state. This groundbreaking discovery holds significant implications for predicting weather anomalies and advancing weather prediction technologies.
A vortex is a rotating region of fluid, such as air or water, characterized by intense rotation. Common examples include typhoons and tornadoes frequently observed in news reports. Professor Choi’s mathematical proof establishes the stability of specific types of vortex structures that can be encountered in real-world fluid flows.
The study builds upon the foundational Euler equation formulated by Leonhard Euler in 1757 to describe the flow of eddy currents. In 1894, British mathematician M. Hill mathematically demonstrated that a ball-shaped vortex could maintain its shape indefinitely while moving along its axis.
Professor Choi’s research confirms that Hill’s spherical vortex maximizes kinetic energy under certain conditions through the application of variational methods. By incorporating functional analysis and partial differential equation theory from mathematical analysis, this study extends previous investigations on two-dimensional fluid flows to encompass three-dimensional fluid dynamics with axial symmetry conditions.
One notable feature identified by Hill is the presence of strong upward airflow at the front of the spherical vortex — an attribute often observed in phenomena like typhoons and tornadoes. Professor Choi’s findings serve as a starting point for further studies involving measurements related to residual time associated with these ascending air currents.
“Research on vortex stability has gained international attention,” stated Professor Choi. “[A]nd it holds long-term potential for advancements in today’s weather forecasting technology.”
Supported by funding from Korea Research Foundation under the Ministry of Science and ICT as well as UNIST, this study was published ahead of official release on July 24th via the online edition of Communications on Pure and Applied Mathematics. More

Research has shown that personal narratives — the stories we tell ourselves about our lives — can play a critical role in identity and help us make sense of the past and present. Research has also shown that by helping people reinterpret narratives, therapists can guide patients toward healthier thoughts and behaviors.
Now, researchers from the Positive Psychology Center at the University of Pennsylvania have tested the ability of ChatGPT-4 to generate individualized personal narratives based on stream-of-consciousness thoughts and demographic details from participants, and showed that people found the language model’s responses accurate.
In a new study in The Journal of Positive Psychology, Abigail Blyler and Martin Seligman found that 25 of the 26 participants rated the AI-generated responses as completely or mostly accurate, 19 rated the narratives as very or somewhat surprising, and 19 indicated they learned something new about themselves. Seligman, the Zellerbach Family Professor of Psychology, is the director of the Positive Psychology Center, and Blyler is his research manager.
“This is a rare moment in the history of scientific psychology: Artificial intelligence now promises much more effective psychotherapy and coaching,” Seligman says.
For each participant, the researchers fed ChatGPT-4 recorded stream-of-consciousness thoughts, which Blyler likened to diary entries with thoughts as simple as “I’m hungry” or “I’m tired.” In a second study published concurrently in The Journal of Positive Psychology, they fed five narratives rated “completely accurate” into ChatGPT-4, asked for specific interventions, and found that the chatbot generated highly plausible coaching strategies and interventions.
“Since coaching and therapy typically involve a great deal of initial time spent fleshing out such an identity, deriving this automatically from 50 thoughts represents a major savings,” the authors write.
Abigail Blyler and Martin Seligman, Zellerbach Family Professor of Psychology and director of Penn’s Positive Psychology Center. More

Solid materials are generally known to be rigid and unmoving, but scientists are turning this idea on its head by exploring ways to incorporate moving parts into solids. This can enable the development of exotic new materials such as amphidynamic crystals — crystals which contain both rigid and mobile components — whose properties can be altered by controlling molecular rotation within the material.
A major challenge to achieving motion in crystals — and in solids in general — is the tightly packed nature of their structure. This restricts dynamic motion to molecules of a limited size. However, a team led by Associate Professor Mingoo Jin from the Institute for Chemical Reaction Design and Discovery (WPI-ICReDD), Hokkaido University has set a size record for such dynamic motion, demonstrating the largest molecular rotor shown to be operational in the solid-state.
A molecular rotor consists of a central rotating molecule that is connected by axis molecules to stationary stator molecules, similar to the way that a wheel and axle are connected to a car frame. Such systems have been previously reported, but the crystalline material in this study features an operational rotor consisting of the molecule pentiptycene, which is nearly 40% larger in diameter than previous rotors in the solid-state, marking a significant advancement.
To enable rotation of such a large molecule, it was necessary to create enough free space within the solid. The team synthesized concave, umbrella-like metal complexes that could shield the rotor molecule from unwanted interactions with other molecules in the crystal. They were able to create sufficient space to accommodate the giant rotor by attaching an especially large, bulky molecule to the metal atom of the stator.
“I got the idea from an egg, which makes a large space and protects its inside with a circular hardcover,” said Jin. “To bring this feature to a molecule, I envisioned encapsulating the rotator space by using bulky concave shaped stators.”
A comparison of experimental and simulated nuclear magnetic resonance spectra of the crystal suggested that the giant molecular rotor rotates in 90-degree intervals at a frequency in the range of 100-400 kHz.
This work expands what is possible for molecular motion in the solid-state. It provides a blueprint for exploring new avenues in the development of amphidynamic crystals, and could lead to the development of new functional materials with unique properties.
“The pentiptycene rotators utilized in this work have several pocket sites,” commented Jin. “This structural feature allows the inclusion of many types of guest compounds including luminophores, which could enable development of highly functional, sophisticated optical or luminescent solid-state materials.” More

The behavior of electrons in liquids plays a big role in many chemical processes that are important for living things and the world in general. For example, slow electrons in liquid have the capacity to cause disruptions in the DNA strand.
But electron movements are extremely hard to capture because they take place within attoseconds: the realm of quintillionths of a second. Since advanced lasers now operate at these timescales, they can offer scientists glimpses of these ultrafast processes via a range of techniques.
An international team of researchers has now demonstrated that it is possible to probe electron dynamics in liquids using intense laser fields and to retrieve the electron’s mean free path — the average distance an electron can travel before colliding with another particle.
“We found that the mechanism by which liquids emit a particular light spectrum, known as the high-harmonic spectrum, is markedly different from the ones in other phases of matter like gases and solids,” said Zhong Yin from Tohoku University’s International Center for Synchrotron Radiation Innovation Smart (SRIS) and co-first author of the paper. “Our findings open the door to a deeper understanding of ultrafast dynamics in liquids.”
Details of the group’s research was published in the journal Nature Physics on September 28, 2023.
Using intense laser fields to generate high-energy photons, a phenomenon known as high-harmonic generation (HHG), is a widespread technique used in many different areas of science, for instance for probing electronic motion in materials, or tracking chemical reactions in time. HHG has been studied extensively in gases and more recently in crystals, but much less is known about liquids.
The research team, which also included researchers from the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) in Hamburg and ETH Zurich, reported on the unique behavior of liquids when irradiated by intense lasers. Until now, almost nothing is known about these light-induced processes in liquids, which surround us everywhere and are present in every chemical reaction. In contrast, scientists have made significant strides in recent years in exploring the behavior of solids under irradiation. Therefore, the experimental team at ETH Zurich developed a unique apparatus to specifically study the interaction of liquids with intense lasers. The researchers discovered a distinctive behavior where the maximum photon energy obtained through HHG in liquids was independent of the laser’s wavelength. What, then, was the responsible factor? More

Cheaper, more efficient lithium-ion batteries could be produced by harnessing previously overlooked high pressures generated during the manufacturing process.
Scientists at the University of Birmingham have discovered that routine ball milling can cause high pressure effects on battery materials in just a matter of minutes, providing a vital additional variable in the process of synthesizing battery materials.
The research (part of the Faraday Institution funded CATMAT project), led by Dr Laura Driscoll, Dr Elizabeth Driscoll and Professor Peter Slater at the University of Birmingham is published in RSC Energy Environmental Science.
The use of ball milling has been a huge area of growth in the lithium-ion battery space to make next generation materials. The process is simple and consists of milling powder compounds with small balls that mix and make the particles smaller, creating high-capacity electrode materials and leading to better performing batteries.
Previous studies had led experts to believe that the synthesis of these materials was caused by localised heating generated in the milling process. But now researchers have found that dynamic impacts from the milling balls colliding with the battery materials create a pressure effect which plays an important role in causing the changes.
Peter Slater, Professor of Materials Chemistry and Co-Director of the Birmingham Centre for Energy Storage at the University of Birmingham, said: “This discovery was almost an accident. We ball milled lithium molybdate as a model system to explore oxygen redox in batteries, and noticed that there was a phase transformation to the high-pressure spinel polymorph, a specific crystal structure that has only previously been made under high-pressure conditions.
“Local heating alone could not explain this transformation. To test this theory, we then ball milled three other battery materials and our findings from these milling experiments reinforced our conclusion that local heating could not be the only reason for these changes.”
The researchers also found that applying heat would cause some compounds to return to their pre-milled state, signifying that an additional variable was at play in the original synthesis: pressure being key. More

Semiconductors are the heart of almost every electronic device. Without semiconductors, our computers would not be able to process and retain data; and LED (light-emitting diode) lightbulbs would lose their ability to shine.
But semiconductor manufacturing requires a lot of energy. Forming semiconductor materials from sand (silicon oxide) consumes a significant amount of heat-intensive energy, at scorching temperatures of around 2,700 degrees Fahrenheit. And the process of purifying and assembling all the raw materials that go into making a semiconductor can take weeks if not months.
A new semiconducting material called “multielement ink” could make that process significantly less heat-intensive and more sustainable. Developed by researchers from Lawrence Berkeley National Laboratory (Berkeley Lab) and UC Berkeley, “multielement ink” is the first “high-entropy” semiconductor that can be processed at low-temperature or room temperature. The breakthrough was recently reported in the journal Nature.
“The traditional way of making semiconductor devices is energy-intensive and one of the major sources of carbon emissions,” said Peidong Yang, the senior author on the study. Yang is a faculty senior scientist in Berkeley Lab’s Materials Sciences Division and professor of chemistry and materials science and engineering at UC Berkeley. “Our new method of making semiconductors could pave the way for a more sustainable semiconductor industry.”
The advance takes advantage of two unique families of semiconducting materials: hard alloys made of high-entropy semiconductors; and a soft, flexible material made of crystalline halide perovskites.
High-entropy materials are solids made of five or more different chemical elements that self-assemble in near-equal proportions into a single system. For many years, researchers have wanted to use high-entropy materials to develop semiconducting materials that self-assemble with minimal energy inputs.
“But high-entropy semiconductors have not been studied to nearly the same extent. Our work could help to significantly fill in that gap of understanding,” said Yuxin Jiang, co-first author and graduate student researcher in the Peidong Yang group with Berkeley Lab’s Materials Sciences Division and the department of chemistry at UC Berkeley. More