Tag Archives: University of California at Los Angeles (UCLA)

Physical neural network based on nanowires can learn and remember ‘on the fly’

A November 1, 2023 news item on Nanowerk announced new work on neuromorphic engineering from Australia,

For the first time, a physical neural network has successfully been shown to learn and remember ‘on the fly’, in a way inspired by and similar to how the brain’s neurons work.

The result opens a pathway for developing efficient and low-energy machine intelligence for more complex, real-world learning and memory tasks.

Key Takeaways
*The nanowire-based system can learn and remember ‘on the fly,’ processing dynamic, streaming data for complex learning and memory tasks.

*This advancement overcomes the challenge of heavy memory and energy usage commonly associated with conventional machine learning models.

*The technology achieved a 93.4% accuracy rate in image recognition tasks, using real-time data from the MNIST database of handwritten digits.

*The findings promise a new direction for creating efficient, low-energy machine intelligence applications, such as real-time sensor data processing.

Nanowire neural network
Caption: Electron microscope image of the nanowire neural network that arranges itself like ‘Pick Up Sticks’. The junctions where the nanowires overlap act in a way similar to how our brain’s synapses operate, responding to electric current. Credit: The University of Sydney

A November 1, 2023 University of Sydney news release (also on EurekAlert), which originated the news item, elaborates on the research,

Published today [November 1, 2023] in Nature Communications, the research is a collaboration between scientists at the University of Sydney and University of California at Los Angeles.

Lead author Ruomin Zhu, a PhD student from the University of Sydney Nano Institute and School of Physics, said: “The findings demonstrate how brain-inspired learning and memory functions using nanowire networks can be harnessed to process dynamic, streaming data.”

Nanowire networks are made up of tiny wires that are just billionths of a metre in diameter. The wires arrange themselves into patterns reminiscent of the children’s game ‘Pick Up Sticks’, mimicking neural networks, like those in our brains. These networks can be used to perform specific information processing tasks.

Memory and learning tasks are achieved using simple algorithms that respond to changes in electronic resistance at junctions where the nanowires overlap. Known as ‘resistive memory switching’, this function is created when electrical inputs encounter changes in conductivity, similar to what happens with synapses in our brain.

In this study, researchers used the network to recognise and remember sequences of electrical pulses corresponding to images, inspired by the way the human brain processes information.

Supervising researcher Professor Zdenka Kuncic said the memory task was similar to remembering a phone number. The network was also used to perform a benchmark image recognition task, accessing images in the MNIST database of handwritten digits, a collection of 70,000 small greyscale images used in machine learning.

“Our previous research established the ability of nanowire networks to remember simple tasks. This work has extended these findings by showing tasks can be performed using dynamic data accessed online,” she said.

“This is a significant step forward as achieving an online learning capability is challenging when dealing with large amounts of data that can be continuously changing. A standard approach would be to store data in memory and then train a machine learning model using that stored information. But this would chew up too much energy for widespread application.

“Our novel approach allows the nanowire neural network to learn and remember ‘on the fly’, sample by sample, extracting data online, thus avoiding heavy memory and energy usage.”

Mr Zhu said there were other advantages when processing information online.

“If the data is being streamed continuously, such as it would be from a sensor for instance, machine learning that relied on artificial neural networks would need to have the ability to adapt in real-time, which they are currently not optimised for,” he said.

In this study, the nanowire neural network displayed a benchmark machine learning capability, scoring 93.4 percent in correctly identifying test images. The memory task involved recalling sequences of up to eight digits. For both tasks, data was streamed into the network to demonstrate its capacity for online learning and to show how memory enhances that learning.

Here’s a link to and a citation for the paper,

Online dynamical learning and sequence memory with neuromorphic nanowire networks by Ruomin Zhu, Sam Lilak, Alon Loeffler, Joseph Lizier, Adam Stieg, James Gimzewski & Zdenka Kuncic. Nature Communications volume 14, Article number: 6697 (2023) DOI: https://doi.org/10.1038/s41467-023-42470-5 Published: 01 November 2023

This paper is open access.

You’ll notice a number of this team’s members are also listed in the citation in my June 21, 2023 posting “Learning and remembering like a human brain: nanowire networks” and you’ll see some familiar names in the citation in my June 17, 2020 posting “A tangle of silver nanowires for brain-like action.”

Questioning or rewriting a ‘central’ dogma of biology?

Answering the question in the head, this December 12, 2023 news item on phys.org calls into question the principle behind how medicines based on antibodies work,

Today, medicines based on antibodies—proteins that fight infection and disease—are prescribed for everything from cancer to COVID-19 to high cholesterol. The antibody drugs are supplied by genetically-engineered cells that function as tiny protein-producing factories in the laboratory.

Meanwhile, researchers have been targeting cancer, injuries to internal organs and a host of other ailments with new strategies in which similarly engineered cells are implanted directly into patients.

These biotechnology applications rely on the principle that altering a cell’s DNA to produce more of the genetic instructions for making a given protein will cause the cell to release more of that protein.

A new UCLA [University of California at Los Angeles] study suggests that—at least in one type of stem cell—the principle doesn’t necessarily hold true.

A December 11, 2023 UCLA news release, which originated the news item, delves further into the topic but first the key points are noted, Note: Links have been removed,

Key takeaways

  • Mesenchymal stem cells, found in bone marrow, secrete therapeutic proteins that could potentially help regenerate damaged tissue.
  • A UCLA study examining these cells challenges the conventional understanding of which genetic instructions prompt the release of these therapeutic proteins.
  • The findings could help advance both regenerative medicine research and the laboratory production of biologic treatments already in use.

The researchers examined mesenchymal stem cells, which reside in bone marrow and can self-renew or develop into bone, fat or muscle cells. Mesenchymal cells secrete a protein growth factor called VEGF-A, which plays a role in regenerating blood vessels and which scientists believe may have the potential to repair damage from heart attacks, kidney injuries, arterial disease in limbs and other conditions.

When the researchers compared the amount of VEGF-A that each mesenchymal cell released with the expression of genes in the same cell that code for VEGF-A, the results were surprising: Gene expression correlated only weakly with the actual secretion of the growth factor.  

The scientists identified other genes better correlating with growth factor secretion, including one that codes for a protein found on the surface of some stem cells. Isolating stem cells with that protein on their surface, the team cultivated a population that secreted VEGF-A prolifically and kept doing so days later.

The findings, published today [December 11, 2023] in Nature Nanotechnology, suggest that a fundamental assumption in biology and biotechnology may be up for reconsideration, said co-corresponding author Dino Di Carlo, the Armond and Elena Hairapetian Professor of Engineering and Medicine at the UCLA Samueli School of Engineering.

“The central dogma has been, you have instructions in the DNA, they’re transcribed to RNA, and then the RNA is translated into protein,” said Di Carlo, who is also a member of UCLA’s California NanoSystems Institute and Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research. “Based on this, many scientists assumed that if you had more RNA, you’d have more protein, and then more protein released from the cell. We questioned that assumption.

“It seems we can’t assume that if a gene is expressed at higher levels, there will be higher secretion of the corresponding protein. We found a clear example where that doesn’t happen, and it opens up a lot of new questions.”

The results could help make the manufacturing of antibody-based treatments more efficient and define new cellular treatments that would be more effective. Knowing the right genetic switches to flip could enable the engineering or selection of extraordinarily productive cells for making or delivering therapies.

The UCLA study was conducted using standard lab equipment augmented with a technology invented by Di Carlo and his colleagues: nanovials, microscopic bowl-shaped hydrogel containers, each of which captures a single cell and its secretions. Leveraging a new nanovial-enabled analytic method, the scientists were able to connect the amount of VEGF-A released by each one of 10,000 mesenchymal stem cells to an atlas mapping tens of thousands of genes expressed by that same cell.

“The ability to link protein secretion to gene expression on the single-cell level holds great promise for the fields of life science research and therapeutic development,” said Kathrin Plath, a UCLA professor of biological chemistry, a member of the Broad Stem Cell Research Center and a co-corresponding author of the study. “Without it, we couldn’t have arrived at the unexpected results we found in this study. Now we have an exciting opportunity to learn new things about the mechanisms underpinning the basic processes of life and use what we learn to advance human health.”

While activation of the genetic instructions for VEGF-A displayed little correlation with release of the protein, the researchers identified a cluster of 153 genes with strong links to VEGF-A secretion. Many of them are known for their function in blood vessel development and wound healing; for others, their function is currently unknown.

One of the top matches encodes a cell-surface protein, IL13RA2, whose purpose is poorly understood. Its exterior location made it simpler for the scientists to use it as a marker and separate those cells from the others. Cells with IL13RA2 showed 30% more VEGF-A secretion than cells that lacked the marker.

In a similar experiment, the researchers kept the separated cells in culture for six days. At the end of that time, cells with the marker secreted 60% more VEGF-A compared to cells without it.

Although therapies based on mesenchymal stem cells have shown promise in laboratory studies, clinical trials with human participants have shown many of these new options to be safe but not effective. The ability to sort for high VEGF-A secreters using IL13RA2 may help turn that tide.

“Identifying a subpopulation that produces more, and markers associated with that population, means you can separate them out very easily,” Di Carlo said. “A very pure population of cells that’s going to produce high levels of your therapeutic protein should make a better therapy.”

Nanovials are available commercially from Partillion Bioscience, a company co-founded by Di Carlo that started up at the CNSI’s on-campus incubator, Magnify.

The first author of the study is Shreya Udani, who earned a doctorate from UCLA in 2023. Other co-authors, all affiliated with UCLA, are staff scientist Justin Langerman; Doyeon Koo, who earned a doctorate in 2023; graduate students Sevana Baghdasarian and Citradewi Soemardy; undergraduate Brian Cheng; Simran Kang, who earned a bachelor’s degree in 2023; and Joseph de Rutte, who earned a doctorate in 2020 and is a co-founder and CEO of Partillion.

The study was supported by the National Institutes of Health and a Stem Cell Nanomedicine Planning Award funded jointly by the CNSI and the Broad Stem Cell Research Center.

Researcher Dino Di Carlo describes his work,

Nanovials, a technology created by UCLA’s Dino Di Carlo and his colleagues, allowed researchers to capture single mesenchymal cells and their secretions. Withouth these vials, which are smaller than the width of a human hair, “we couldn’t have arrived at the unexpected results we found in this study,” said UCLA’s Kathrin Plath.

Here’s a link to and a citation for the paper,

Associating growth factor secretions and transcriptomes of single cells in nanovials using SEC-seq by Shreya Udani, Justin Langerman, Doyeon Koo, Sevana Baghdasarian, Brian Cheng, Simran Kang, Citradewi Soemardy, Joseph de Rutte, Kathrin Plath & Dino Di Carlo. Nature Nanotechnology (2023) DOI: https://doi.org/10.1038/s41565-023-01560-7 Published: 11 December 2023

This paper is behind a paywall.

As for the two companies mentioned in the news release, you find Partillion Bioscience here and Magnify at CNSI here.

Reversing lower limb paralysis

This regenerative treatment is at a very early stage, which means the Swiss researchers have tried it on mice as you can see in the following video (runtime: 2 mins. 15 secs.). Towards the end of the video, researcher Grégoire Courtine cautions there are many hurdles before this could be used in humans, if ever,

A September 22, 2023 Ecole Polytechnique Fédérale de Lausanne (EPFL) press release (also on EurekAlert but published September 21, 2023) by Emmanuel Barraud, describes the work in more detail,

When the spinal cords of mice and humans are partially damaged, the initial paralysis is followed by the extensive, spontaneous recovery of motor function. However, after a complete spinal cord injury, this natural repair of the spinal cord doesn’t occur and there is no recovery. Meaningful recovery after severe injuries requires strategies that promote the regeneration of nerve fibers, but the requisite conditions for these strategies to successfully restore motor function have remained elusive.

“Five years ago, we demonstrated that nerve fibers can be regenerated across anatomically complete spinal cord injuries,” says Mark Anderson, a senior author of the study. “But we also realized this wasn’t enough to restore motor function, as the new fibers failed to connect to the right places on the other side of the lesion.” Anderson is the director of Central Nervous System Regeneration at .NeuroRestore and a scientist at the Wyss Center for Bio and Neuroengineering.

Working in tandem with peers at UCLA [University of California at Los Angeles] and Harvard Medical School, the scientists used state-of-the-art equipment at EPFL’s Campus Biotech facilities in Geneva to run in-depth analyses and identity which type of neuron is involved in natural spinal-cord repair after partial spinal cord injury. “Our observations using single-cell nuclear RNA sequencing not only exposed the specific axons that must regenerate, but also revealed that these axons must reconnect to their natural targets to restore motor function,” says Jordan Squair, the study’s first author. The team’s findings appear in the 22 September 2023 issue of Science.

Towards a combination of approaches

Their discovery informed the design of a multipronged gene therapy. The scientists activated growth programs in the identified neurons in mice to regenerate their nerve fibers, upregulated specific proteins to support the neurons’ growth through the lesion core, and administered guidance molecules to attract the regenerating nerve fibers to their natural targets below the injury. “We were inspired by nature when we designed a therapeutic strategy that replicates the spinal-cord repair mechanisms occurring spontaneously after partial injuries,” says Squair.

Mice with anatomically complete spinal cord injuries regained the ability to walk, exhibiting gait patterns that resembled those quantified in mice that resumed walking naturally after partial injuries. This observation revealed a previously unknown condition for regenerative therapies to be successful in restoring motor function after neurotrauma. “We expect that our gene therapy will act synergistically with our other procedures involving electrical stimulation of the spinal cord,” says Grégoire Courtine, a senior author of the study who also heads .NeuroRestore together with Jocelyne Bloch. “We believe a complete solution for treating spinal cord injury will require both approaches – gene therapy to regrow relevant nerve fibers, and spinal stimulation to maximize the ability of both these fibers and the spinal cord below the injury to produce movement.”

While many obstacles must still be overcome before this gene therapy can be applied in humans, the scientists have taken the first steps towards developing the technology necessary to achieve this feat in the years to come.

Here’s a link to and a citation for the paper,

Recovery of walking after paralysis by regenerating characterized neurons to their natural target region by Jordan W. Squair, Marco Milano, Alexandra de Coucy, Matthieu Gautier, Michael A. Skinnider, Nicholas D. James, Newton Cho, Anna Lasne, Claudia Kathe,Thomas H. Hutson, Steven Ceto, Laetitia Baud, Katia Galan, Viviana Aureli, Achilleas Laskaratos, Quentin Barraud, Timothy J. Deming, Richie E. Kohman, Bernard L. Schneider, Zhigang He, Jocelyne Bloch, Michael V. Sofroniew, Gregoire Courtine, and Mark A. Anderson. Science 21 Sep 2023 Vol 381, Issue 6664 pp. 1338-1345 DOI: 10.1126/science.adi641

This paper is behind a paywall.

This March 25, 2015 posting, “Spinal cords, brains, implants, and remote control,” features some research from EPFL researchers whose names you might recognize from this posting’s research paper.

Mentioned in the press release, the Swiss research centre website for NeuroRestore is here.

Need to improve oversight on chimeric human-animal research

It seems chimeras are of more interest these days. In all likelihood that has something to do with the fellow who received a transplant of a pig’s heart in January 2022 (he died in March 2022).

For those who aren’t familiar with the term, a chimera is an entity with two different DNA (deoxyribonucleic acid) identities. In short, if you get a DNA sample from the heart, it’s different from a DNA sample obtained from a cheek swab. This contrasts with a hybrid such as a mule (donkey/horse) whose DNA samples show a consisted identity throughout its body.

A December 12, 2022 The Hastings Center news release (also on EurekAlert) announces a special report,

A new report on the ethics of crossing species boundaries by inserting human cells into nonhuman animals – research surrounded by debate – makes recommendations clarifying the ethical issues and calling for improved oversight of this work.

The report, “Creating Chimeric Animals — Seeking Clarity On Ethics and Oversight,” was developed by an interdisciplinary team, with funding from the National Institutes of Health. Principal investigators are Josephine Johnston and Karen Maschke, research scholars at The Hastings Center, and Insoo Hyun, director of the Center for Life Sciences and Public Learning at the Museum of Life Sciences in Boston, formerly of Case Western Reserve University.

Advances in human stem cell science and gene editing enable scientists to insert human cells more extensively and precisely into nonhuman animals, creating “chimeric” animals, embryos, and other organisms that contain a mix of human and nonhuman cells.

Many people hope that this research will yield enormous benefits, including better models of human disease, inexpensive sources of human eggs and embryos for research, and sources of tissues and organs suitable for transplantation into humans. 

But there are ethical concerns about this type of research, which raise questions such as whether the moral status of nonhuman animals is altered by the insertion of human stem cells, whether these studies should be subject to additional prohibitions or oversight, and whether this kind of research should be done at all.

The report found that:

Animal welfare is a primary ethical issue and should be a focus of ethical and policy analysis as well as the governance and oversight of chimeric research.

Chimeric studies raise the possibility of unique or novel harms resulting from the insertion and development of human stem cells in nonhuman animals, particularly when those cells develop in the brain or central nervous system.

Oversight and governance of chimeric research are siloed, and public communication is minimal. Public communication should be improved, communication between the different committees involved in oversight at each institution should be enhanced, and a national mechanism created for those involved in oversight of these studies. 

Scientists, journalists, bioethicists, and others writing about chimeric research should use precise and accessible language that clarifies rather than obscures the ethical issues at stake. The terms “chimera,” which in Greek mythology refers to a fire-breathing monster, and “humanization” are examples of ethically laden, or overly broad language to be avoided.

The Research Team

The Hastings Center

• Josephine Johnston
• Karen J. Maschke
• Carolyn P. Neuhaus
• Margaret M. Matthews
• Isabel Bolo

Case Western Reserve University
• Insoo Hyun (now at Museum of Science, Boston)
• Patricia Marshall
• Kaitlynn P. Craig

The Work Group

• Kara Drolet, Oregon Health & Science University
• Henry T. Greely, Stanford University
• Lori R. Hill, MD Anderson Cancer Center
• Amy Hinterberger, King’s College London
• Elisa A. Hurley, Public Responsibility in Medicine and Research
• Robert Kesterson, University of Alabama at Birmingham
• Jonathan Kimmelman, McGill University
• Nancy M. P. King, Wake Forest University School of Medicine
• Geoffrey Lomax, California Institute for Regenerative Medicine
• Melissa J. Lopes, Harvard University Embryonic Stem Cell Research Oversight Committee
• P. Pearl O’Rourke, Harvard Medical School
• Brendan Parent, NYU Grossman School of Medicine
• Steven Peckman, University of California, Los Angeles
• Monika Piotrowska, State University of New York at Albany
• May Schwarz, The Salk Institute for Biological Studies
• Jeff Sebo, New York University
• Chris Stodgell, University of Rochester
• Robert Streiffer, University of Wisconsin-Madison
• Lorenz Studer, Memorial Sloan Kettering Cancer Center
• Amy Wilkerson, The Rockefeller University

Here’s a link to and a citation for the report,

Creating Chimeric Animals: Seeking Clarity on Ethics and Oversight edited by Karen J. Maschke, Margaret M. Matthews, Kaitlynn P. Craig, Carolyn P. Neuhaus, Insoo Hyun, Josephine Johnston, The Hastings Center Report Volume 52, Issue S2 (Special Report), November‐December 2022 First Published: 09 December 2022

This report is open access.

Keep your building cool with super paint

As temperatures rise and the Arctic melts, scientists are searching for ways to keep us and our buildings cool without adding unduly to our current problems. A July 8, 2020 University of California at Los Angeles news release (also on EurekAlert) announces a new paint,

A research team led by UCLA materials scientists has demonstrated ways to make super white paint that reflects as much as 98% of incoming heat from the sun. The advance shows practical pathways for designing paints that, if used on rooftops and other parts of a building, could significantly reduce cooling costs, beyond what standard white ‘cool-roof’ paints can achieve.

The findings, published online in Joule, are a major and practical step towards keeping buildings cooler by passive daytime radiative cooling — a spontaneous process in which a surface reflects sunlight and radiates heat into space, cooling down to potentially sub-ambient temperatures. This can lower indoor temperatures and help cut down on air conditioner use and associated carbon dioxide emissions.

“When you wear a white T-shirt on a hot sunny day, you feel cooler than if you wore one that’s darker in color — that’s because the white shirt reflects more sunlight and it’s the same concept for buildings,” said Aaswath Raman, an assistant professor of materials science and engineering at UCLA Samueli School of Engineering, and the principal investigator on the study. “A roof painted white will be cooler inside than one in a darker shade. But those paints also do something else: they reject heat at infrared wavelengths, which we humans cannot see with our eyes. This could allow buildings to cool down even more by radiative cooling.”

The best performing white paints currently available typically reflect around 85% of incoming solar radiation. The remainder is absorbed by the chemical makeup of the paint. The researchers showed that simple modifications in a paint’s ingredients could offer a significant jump, reflecting as much as 98% of incoming radiation.

Current white paints with high solar reflectance use titanium oxide. While the compound is very reflective of most visible and near-infrared light, it also absorbs ultraviolet and violet light. The compound’s UV absorption qualities make it useful in sunscreen lotions, but they also lead to heating under sunlight – which gets in the way of keeping a building as cool as possible.

The researchers examined replacing titanium oxide with inexpensive and readily available ingredients such as barite, which is an artist’s pigment, and pow[d]ered polytetrafluoroethylene, better known as Teflon. These ingredients help paints reflect UV light. The team also made further refinements to the paint’s formula, including reducing the concentration of polymer binders, which also absorb heat.

“The potential cooling benefits this can yield may be realized in the near future because the modifications we propose are within the capabilities of the paint and coatings industry,” said UCLA postdoctoral scholar Jyotirmoy Mandal, a Schmidt Science Fellow working in Raman’s research group and the co-corresponding author on the research.

Beyond the advance, the authors suggested several long-term implications for further study, including mapping where such paints could make a difference, studying the effect of pollution on radiative cooling technologies, and on a global scale, if they could make a dent on the earth’s own ability to reflect heat from the sun.

The researchers also noted that many municipalities and governments, including the state of California and New York City, have started to encourage cool-roof technologies for new buildings.

“We hope that the work will spur future initiatives in super-white coatings for not only energy savings in buildings, but also mitigating the heat island effects of cities, and perhaps even showing a practical way that, if applied on a massive, global scale could affect climate change,” said Mandal, who has studied cooling paint technologies for several years. “This would require a collaboration among experts in diverse fields like optics, materials science and meteorology, and experts from the industry and policy sectors.”

Here’s a link (also in the news release) to and a citation for the paper,

Paints as a Scalable and Effective Radiative Cooling Technology for Buildings by Jyotirmoy Mandal, Yuan Yang, Nanfang Yu, Aaswath P. Raman. Joule DOI: https://doi.org/10.1016/j.joule.2020.04.010 Published: May 29, 2020

This paper is behind a paywall.