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MRIs, Mozart and the wonders of mathematics

If you鈥檝e had an MRI in recent years, you have UCLA mathematician and Fields Medal winner Terence Tao to thank for the technology. His foundational work in compressed sensing, conducted with Stanford professor Emmanuel Cand猫s, paved the way for clinical techniques that use complex algorithms to create amazingly precise images from a tiny amount of data 鈥� cutting down the time and cost of the process and expanding its availability.

Tao, dubbed the 鈥淢ozart of math鈥� and widely considered the world鈥檚 greatest living mathematician, has reshaped vast areas of mathematics, from harmonic analysis and partial differential equations to algebraic geometry, number theory and combinatorics 鈥� and he鈥檚 now exploring the frontier where math meets artificial intelligence.

And while he understands that these mathematical topics might fly over the heads of most people, he stresses that the 鈥減ure math鈥� research he and his colleagues perform, although seemingly esoteric, can yield results that ripple far beyond the chalkboard, informing tomorrow鈥檚 advances in science, technology and beyond.

鈥淢athematicians often work on pure problems that do not have any applications for 20 years,鈥� he has said, noting that Einstein鈥檚 theory of relativity ultimately hinged on math that had been developed decades earlier. "Contributions to tangible technological advances are subtle and indirect, but without such basic research, many advances would have taken far longer to be developed, and some may not have been pursued at all.鈥�

Tao鈥檚 own discoveries, assisted by a series of collaborators, are pushing those advances forward. Beyond his work in compressed sensing, he and a colleague have made significant advances on a centuries-old question about the hidden structure of prime numbers 鈥� an area of math that informs the backbone of modern encryption and digital security, allowing people to use credit and bank cards without fear. And his explorations of the math behind fluid dynamics could eventually reshape how we model weather, assess turbulence in air and water, optimize industrial fluid systems, and study plasma in stars.

Now, Tao is pushing mathematics into the age of artificial intelligence, exploring how AI can support and quicken mathematical discovery by supporting collaborations among mathematicians, computer scientists, logicians and even the public, making research faster, cheaper and more efficient and, potentially, connecting abstract theory more quickly with real-world technologies.

Tao recently saw his National Science Foundation research funding 鈥� along with funding for UCLA鈥檚 Institute of Pure and Applied Mathematics, where he is director of special projects 鈥� frozen. And in the wake of these suspensions, he stresses that the stakes for UCLA and the nation aren鈥檛 just academic, particularly when it comes to areas like cryptography and secure systems.

鈥淚t is important to do this kind of research,鈥� he says. 鈥淚f we don鈥檛, it鈥檚 possible that an adversary could actually discover these weaknesses that we are not looking for at all.鈥�

The lives and policies behind the data

Martha Bailey is breathing history into data. The UCLA economic historian, demographer and labor economist is stitching together the rich tapestry of American life across four generations through her visionary leadership of LIFE鈥慚, a unique data infrastructure project linking millions of birth, marriage and death records with census information on everything from household size and wages to educational attainment.

The goal? To help researchers across the country better ask and answer big questions about how economic, educational, health-related and environmental circumstances and policies have shaped people鈥檚 lives from the cradle to the grave since the dawn of the 20th century.

鈥淭he biggest changes in our society and economy don鈥檛 play out over a decade,鈥� says Bailey, who also directs the California Center or Population Research at UCLA and is a research associate at the National Bureau of Economic Research. 鈥淭hey play out over multiple generations as part of ongoing, slow-moving transformations.鈥�

That鈥檚 why the datasets of LIFE-M (short for Longitudinal, Intergenerational Family Electronic Micro-database) are so revolutionary. With the help of machine learning, the project compiles reams of intergenerational public information that present a grand survey of life changes 鈥� from great-grandparents born at the turn of the century to their grandchildren born in the 1970s.

For instance, Bailey says, LIFE-M data clearly reveal how government investment in education has boosted economic opportunity 鈥� from the early 20th century, when public funding of K鈥�12 schools allowed lower-income children to escape the circumstances of their birth, to the later years of the century, when investment in public higher education further encouraged mobility, reducing the role of family privilege.

Similarly, by compiling data over multiple generations in a particular community, the project offers an expansive picture of people鈥檚 quality of health and aging. This can be particularly helpful, Bailey says, when scholars are assessing how environmental exposures may contribute to cognitive conditions like Alzheimer鈥檚 and Parkinson鈥檚 over time or when they鈥檙e tracking the evolution of a cancer cluster in a newly industrialized area.

鈥淟ike roads and bridges,鈥� she says, 鈥渄ata infrastructure is foundational for answering fundamental questions about health and social policy.鈥�

LIFE-M, which has been used by hundreds of social scientists, took a decade to set up and was seeded with National Science Foundation funding. Yet just as the project planned to expand its dataset from two states to nine with the help of a National Institute on Aging grant, that funding was frozen. Important research projects have been put on hold, Bailey notes, but it鈥檚 the state鈥檚 larger educational enterprise that is really in peril.

鈥淭he funding and expertise of our researchers spills over into a top-notch education for students, who go onto all types of professions. It鈥檚 one big package; research and teaching are deeply interrelated. Losing funds leads to losing the best faculty and best graduate students to other universities and countries, which is a huge loss for California鈥檚 public higher education.鈥�

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Researchers make progress toward a 鈥榩ill鈥� for stroke recovery

Imagine a medicine that could help your brain heal after a stroke 鈥� without the grueling hours of physical therapy. That鈥檚 the promise of a new discovery by UCLA researchers who have identified a drug candidate that successfully mimics the effects of stroke rehabilitation in mice.

Stroke is the leading cause of long-term disability in adults, leaving many survivors with damaged neural connections that hinder their movement and coordination. Traditional rehabilitation techniques don鈥檛 always work, primarily because many patients can鈥檛 sustain the physical intensity required for recovery, says neuroscientist Dr. S. Thomas Carmichael, who chairs UCLA鈥檚 Department of Neurology.

Working with stroke patients and mouse models, Carmichael and his team discovered that brain cells located away from the actual stroke site 鈥� cells known as parvalbumin neurons 鈥� get disconnected from other neurons. These special neurons generate vital gamma oscillations, brain rhythms that link neurons together to synchronize coordinated motion. Physical therapy in both mice and humans restores these rhythms, they found, but developing a drug that replicates that recovery was the next frontier.

Through meticulous research, the team identified a drug called DDL-920 鈥� developed in the UCLA lab of Dr. Varghese John 鈥� that showed remarkable results, restoring movement control in mice nearly as effectively as physical rehabilitation.

While the findings are promising, further research is crucial. The team will need to conduct safety and efficacy studies before human trials can begin, Carmichael says. But the research offers genuine hope for the future. If DDL-920 proves safe and effective in humans, it could revolutionize stroke recovery 鈥� potentially making rehabilitation as simple as taking a pill.

鈥淭he goal is to have a medicine that stroke patients can take that produces the effects of rehabilitation,鈥� Carmichael says. 鈥淩ehabilitation after stroke is limited in its actual effects because most patients cannot sustain the rehab intensity needed for stroke recovery 鈥� We need to move rehabilitation into an era of molecular medicine.鈥�

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How Andrea Ghez unveiled the secrets of the stars

When world-renowned UCLA astrophysicist Andrea Ghez set out to map the heart of our galaxy, skeptics told her it couldn鈥檛 be done. Today she stands among science鈥檚 elite: a 2020 Nobel laureate 鈥� just the fourth woman ever awarded the prize in physics 鈥� for her pioneering discovery of the supermassive black hole at the center of the Milky Way.

Ghez鈥檚 supermassive discovery has transformed our understanding of the formation, growth and dynamics of galaxies and deepened what we know about the laws of physics and the universe.

Her early fascination with the mysterious center of the Milky Way led her to develop advanced imaging tools to peer through cosmic dust and distortion.

鈥淗ow do you observe something you can鈥檛 see?鈥� asks Ghez, UCLA鈥檚 Lauren B. Leichtman and Arthur E. Levine Professor of Astrophysics. 鈥淭hat鈥檚 an essential question when you want to find and study black holes, because black holes are objects whose pull of gravity is so intense that nothing can escape them 鈥� not even light.鈥�

Because Earth鈥檚 atmosphere blurs our view of the rest of the universe 鈥� Ghez likens it to looking at a pebble through rippling water 鈥� she helped pioneer adaptive optics, a technology that corrects these distortions in real time, delivering crystal-clear images of stars swirling around the galactic center.

Those tools allowed her to track these stellar orbits for years at the W.M. Keck Observatory in Hawaii, with support from UCLA, the University of California, the National Science Foundation and other sources. Ghez and her team were ultimately able to gather compelling proof: a massive, invisible object 鈥� 4 million times the sun鈥檚 mass 鈥� holding those stars by gravitational force. It was the clearest evidence yet of a supermassive black hole.

Ghez describes how through perseverance she was able to bring together more than a hundred collaborators from around the world to ask and answer important questions. And that same perseverance helped sustain her through the initial skepticism about her project for developing methods to find and study black holes 鈥� and ultimately secure more funding. On that score, she says, she has a favorite saying: Every challenge is an opportunity.

鈥淥ur project didn鈥檛 seem important to a lot of people, but the University of California and UCLA gave us the tools to look deep into the universe, and we were able to bring something incredible into focus,鈥� she says. 鈥淲e showed the world something that鈥檚 impossible to see directly and discovered more questions than answers. And that鈥檚 what UCLA does every day. We ask questions. We explore those things still shrouded in darkness, and we bring new knowledge and understanding into focus. And I鈥檓 so proud and grateful to be part of this incredible institution.鈥�

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What鈥檚 the trick to aging well?

If you鈥檙e curious about the answer, you鈥檙e already on the right track, says UCLA psychology professor Alan Castel.

Castel and an international team of psychology researchers have shown that curiosity doesn鈥檛 have to fade with age 鈥� certain types of curiosity can persist into later life and actually increase. And better yet, they say, older adults who maintain their curiosity and are eager to learn new things relevant to their interests may be able to offset or even prevent cognitive decline and Alzheimer鈥檚 disease. On the other hand, those whose curiosity is muted and who display general disinterest may be at risk for dementia.

The researchers distinguished between two types of curiosity. The first, 鈥渢rait curiosity,鈥� is a personality trait and reflects a person鈥檚 general curiosity and disposition toward learning. The second, 鈥渟tate curiosity,鈥� is the momentary feeling of curiosity people experience when they鈥檙e asked about specific topics or something grabs their attention; prior studies suggested this form of curiosity declines as people get older. But Castel鈥檚 study, supported by federal funding, suggested a different story.

It was trait curiosity, the researchers found, that generally declined with age. State curiosity dipped in young adulthood and hit a low in midlife 鈥� but then increased sharply after middle age and continued upward well into older age. In fact, older adults in general showed a rising enthusiasm for learning about topics that genuinely interested them.

The reason for the shift? It might be tied to life鈥檚 shifting demands, Castel says. Midlife often comes with heavier responsibilities like careers and families, which limit the time and space for intellectual exploration. But as these pressures ease, later life offers the freedom to return to passions and curiosities.

And importantly, maintaining a curious mindset isn鈥檛 just enriching 鈥� it may also support lifelong cognitive health. Adults who stay curious, Castel says, tend to remain mentally sharp. He recommends that people keep the spark alive by exploring things that matter to them, engaging with people who share their curiosity, taking classes and attending lectures.

鈥淎s we get older, we don鈥檛 want to stop learning; we鈥檙e just more selective about what we want to learn,鈥� Castel says. 鈥淵ou see this in the context of lifelong learning: A lot of older adults will go back to take classes or pick up hobbies or engage in bird watching. I think it shows that this level of curiosity, if maintained, can really keep us sharp as we age.鈥�

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The true cost of abandoning science

What happens when the government turns its back on scientific research? UCLA鈥檚 Steven Furlanetto, a professor of physics and astronomy who studies ancient galaxies, powerfully and eloquently addressed this question in a recent opinion column for the Los Angeles Times.

Since the end of World War II, thanks in large part to substantial investment in research by the federal government, the United States has been the epicenter of global science and curiosity-driven investigation 鈥� in astronomy, quantum materials, evolutionary biology, biomedical sciences and many other fields.

But with recent events, Furlanetto sounds the alarm bell: America鈥檚 status, he says, will not survive the federal government鈥檚 massive funding cuts to science 鈥� both to basic scientific research at universities and laboratories and to scientific staff at federal agencies like the National Science Foundation, NASA and the National Park Service.

The debilitating cuts, he argues, 鈥渨ill choke off new technologies before they are only half an idea, leave fundamental questions about the universe unanswered and chase a generation of scientists to other countries.鈥�

Furlanetto credits American taxpayers with many of the country鈥檚 postwar scientific advancements. These investments, provided through the government, have led to public goods like new technologies, ways to mitigate natural disasters (like the Los Angeles wildfires or recent floods in Texas) and strong economic growth. He points out that basic science research accounts for only one-half of 1% of the federal government鈥檚 budget 鈥� outside of Social Security and Medicare 鈥� and slashing science funding is destructive to our nation鈥檚 mission, while not very cost-saving.

America faces a crucial choice, he says: We can 鈥渞emain at the vanguard of scientific inquiry through sound investment, or to cede our leadership and watch others answer the big questions that have confounded humanity for millennia 鈥� and reap the rewards and prestige. Only one of those options will make the future America great.鈥�

A 鈥榤iracle鈥� drug for leukemia

In 1995, Melvin Mann, a major in the U.S. Army and the father of an 8-year-old daughter, was diagnosed with a rare and deadly blood cancer called chronic myelogenous leukemia. Unable to find a suitable bone marrow donor, he was told he had only a few years to live.

Three years later and barely able to get out of bed, Mann enrolled in a clinical trial testing an experimental drug called a tyrosine kinase inhibitor. 鈥淭hat was the drug that saved my life,鈥� he recalls. Within 10 months of starting treatment, he had the strength to complete a marathon.

That 鈥渕iracle鈥� drug, eventually marketed as Gleevec (and known generically as imatinib), was the world鈥檚 first targeted therapy for chronic myelogenous leukemia and acute lymphoblastic leukemia and would become one of the most successful leukemia drugs in history. And much of the crucial research that led to Gleevec鈥檚 development was conducted by physician-scientist Dr. Owen Witte at UCLA with federal funding.

In the 1980s, Witte, a distinguished professor of microbiology, immunology and molecular genetics and founding director emeritus of UCLA鈥檚 Broad Stem Cell Research Center, found that a specific enzymatic activity in a cancer gene known as BCR-ABL played a role in certain types of leukemia.

That discovery defined a molecular target for these leukemias and helped usher in a new era of targeted cancer therapies 鈥� therapies that attack specific proteins, enzymes and genes that cancer cells need to grow and spread, while leaving healthy cells alone. In the case of chronic myelogenous leukemia, Gleevec inhibits the cancer-causing effects of a chemical called tyrosine kinase, a protein in the body that drives cell division.聽

Since then, Witte鈥檚 ongoing discoveries have helped to fundamentally reshape the treatment of leukemias, lymphomas and other cancers.

For Melvin Mann, Gleevec was a godsend. He was able to be there as his daughter got her driver鈥檚 license and graduated from high school, college and eventually medical school. And hundreds of thousands of chronic myelogenous leukemia patients worldwide 鈥� including the 9,000 diagnosed each year in the U.S. 鈥� have similar stories. After all, today they can expect to live long, healthy lives.

Witte acknowledges that he was one of many who contributed to the development of tyrosine kinase inhibitors 鈥� he and other scientists in academic and government labs across the country worked for decades, and federal funding for exploratory research powered their progress. The pharmaceutical industry now makes tyrosine kinase inhibitors for dozens of diseases, including other forms of cancer, autoimmune conditions and metabolic disease.

鈥淢illions of people are taking these medicines and are walking around leading relatively normal lives, instead of getting sicker and dying,鈥� Witte says. 鈥淎nd those pharmaceutical companies are keeping a lot of people employed and generating a lot of economic activity. I could not imagine a better use of federal funding than that.鈥�

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Eating fish 鈥� without the fear of mercury

If you love seafood but worry about the effects of mercury, UCLA has good news. New research by university scientists and colleagues suggests that a specially engineered probiotic could one day help your body block toxic mercury before it causes harm 鈥� without forcing you to give up your favorite sushi dish.

It鈥檚 particularly welcome news for pregnant women 鈥� toxic mercury has been shown to pose a serious threat to the developing fetus 鈥� as well as those who subsist on a largely fish-based diet.

So what鈥檚 the connection between fish and mercury? Methylmercury, a highly toxic form of mercury, forms when environmental mercury 鈥� released primarily by human activities like coal burning, artisanal gold mining, smelting and industrial waste 鈥� makes its way into bodies of water. This contaminant then increases in concentration as it moves up the marine food chain. Larger predators like bluefin tuna 鈥� and later, the humans consuming the fish 鈥� acquire all the mercury accumulated by the previous links in the chain. People who eat food with high mercury levels are at greater risk of mercury poisoning and birth defects.

With funding from the National Science Foundation and other sources, scientists from UCLA and UC San Diego鈥檚 Scripps Institution of Oceanography engineered a common human gut bacterium by inserting genes that encode methylmercury鈥恉etoxifying enzymes. They then administered the microbe as a probiotic to mice that had been fed a diet rich in bluefin tuna. They found that the microbe detoxified methylmercury in the guts of the mice and dramatically reduced the amount of the contaminant that reached other tissues, such as the brain and liver.

Importantly, pregnant mice and their fetuses displayed significantly reduced methylmercury accumulation and lower signs of brain toxicity, pointing to potential benefits for maternal and fetal health.

While the findings are still in early stages, the researchers are optimistic. With continued funding and development, they plan to improve the probiotic鈥檚 effectiveness and ensure it can be safely translated for human use with continued funding and development.

The study鈥檚 senior author, Elaine Hsiao, an associate professor and director of the UCLA Goodman鈥揕uskin Microbiome Center, envisions the possibility that one day people will simply be able to take a probiotic pill that will offset the risk of too much mercury 鈥� preserving the benefits of fish consumption in diets around the world and protecting pregnant women from harm.

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