Variability Keeps The Body In Balance

Although the heart beats out a very familiar "lub-dub" pattern that speeds up or slows down as our activity increases or decreases, the pattern itself isn't as regular as you might think. In fact, the amount of time between heartbeats can vary even at a "constant" heart rate—and that variability, doctors have found, is a good thing.

Reduced heart rate variability (HRV) has been found to be predictive of a number of illnesses, such as congestive heart failure and inflammation. For athletes, a drop in HRV has also been linked to fatigue and overtraining. However, the underlying physiological mechanisms that control HRV—and exactly why this variation is important for good health—are still a bit of a mystery.

By combining heart rate data from real athletes with a branch of mathematics called control theory, a collaborative team of physicians and Caltech researchers from the Division of Engineering and Applied Science have now devised a way to better understand the relationship between HRV and health—a step that could soon inform better monitoring technologies for athletes and medical professionals.

The work was published in the August 19 print issue of the Proceedings of the National Academy of Sciences.

To run smoothly, complex systems, such as computer networks, cars, and even the human body, rely upon give-and-take connections and relationships among a large number of variables; if one variable must remain stable to maintain a healthy system, another variable must be able to flex to maintain that stability. Because it would be too difficult to map each individual variable, the mathematics and software tools used in control theory allow engineers to summarize the ups and downs in a system and pinpoint the source of a possible problem.

Researchers who study control theory are increasingly discovering that these concepts can also be extremely useful in studies of the human body. In order for a body to work optimally, it must operate in an environment of stability called homeostasis. When the body experiences stress—for example, from exercise or extreme temperatures—it can maintain a stable blood pressure and constant body temperature in part by dialing the heart rate up or down. And HRV plays an important role in maintaining this balance, says study author John Doyle, the Jean-Lou Chameau Professor of Control and Dynamical Systems, Electrical Engineering, and Bioengineering.

"A familiar related problem is in driving," Doyle says. "To get to a destination despite varying weather and traffic conditions, any driver—even a robotic one—will change factors such as acceleration, braking, steering, and wipers. If these factors suddenly became frozen and unchangeable while the car was still moving, it would be a nearly certain predictor that a crash was imminent. Similarly, loss of heart rate variability predicts some kind of malfunction or 'crash,' often before there are any other indications," he says.

To study how HRV helps maintain this version of "cruise control" in the human body, Doyle and his colleagues measured the heart rate, respiration rate, oxygen consumption, and carbon dioxide generation of five healthy young athletes as they completed experimental exercise routines on stationary bicycles.

By combining the data from these experiments with standard models of the physiological control mechanisms in the human body, the researchers were able to determine the essential tradeoffs that are necessary for athletes to produce enough power to maintain an exercise workload while also maintaining the internal homeostasis of their vital signs.

"For example, the heart, lungs, and circulation must deliver sufficient oxygenated blood to the muscles and other organs while not raising blood pressure so much as to damage the brain," Doyle says. "This is done in concert with control of blood vessel dilation in the muscles and brain, and control of breathing. As the physical demands of the exercise change, the muscles must produce fluctuating power outputs, and the heart, blood vessels, and lungs must then respond to keep blood pressure and oxygenation within narrow ranges."

Once these trade-offs were defined, the researchers then used control theory to analyze the exercise data and found that a healthy heart must maintain certain patterns of variability during exercise to keep this complicated system in balance.  Loss of this variability is a precursor of fatigue, the stress induced by exercise. Today, some HRV monitors in the clinic can let a doctor know when variability is high or low, but they provide little in the way of an actionable diagnosis.

Because monitors in hospitals can already provide HRV levels and dozens of other signals and readings, the integration of such mathematical analyses of control theory into HRV monitors could, in the future, provide a way to link a drop in HRV to a more specific and treatable diagnosis. In fact, one of Doyle's students has used an HRV application of control theory to better interpret traditional EKG signals.

Control theory could also be incorporated into the HRV monitors used by athletes to prevent fatigue and injury from overtraining, he says.

"Physicians who work in very data-intensive settings like the operating room or ICU are in urgent need of ways to rapidly and acutely interpret the data deluge," says Marie Csete, MD (PhD, '00), chief scientific officer at the Huntington Medical Research Institutes and a coauthor on the paper. "We hope this work is a first step in a larger research program that helps physicians make better use of data to care for patients."

This study is not the first to apply control theory in medicine. Control theory has already informed the design of a wearable artificial pancreas for type 1 diabetic patients and an automated prototype device that controls the administration of anesthetics during surgery. Nor will it be the last, says Doyle, whose sights are next set on using control theory to understand the progression of cancer.

"We have a new approach, similarly based on control of networks, that organizes and integrates a bunch of new ideas floating around about the role of healthy stroma—non-tumor cells present in tumors—in promoting cancer progression," he says.

"Based on discussions with Dr. Peter Lee at City of Hope [a cancer research and treatment center], we now understand that the non-tumor cells interact with the immune system and with chemotherapeutic drugs to modulate disease progression," Doyle says. "And I'm hoping there's a similar story there, where thinking rigorously about the tradeoffs in development, regeneration, inflammation, wound healing, and cancer will lead to new insights and ultimately new therapies."

Other Caltech coauthors on the study include former graduate students Na Li (PhD '13) now an assistant professor at Harvard; Somayeh Sojoudi (PhD '12), currently at NYU; and graduate students Chenghao Simon Chien and Jerry Cruz. Other collaborators on the study were Benjamin Recht, a former postdoctoral scholar in Doyle's lab and now an assistant professor at UC Berkeley; Daniel Bahmiller, a clinician training in public health; and David Stone, MD, an expert in ICU medicine from the University of Virginia School of Medicine.

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Remembering Frank Marble


Frank Earl Marble (Eng '47, PhD '48), Caltech's Richard L. and Dorothy M. Hayman Professor of Mechanical Engineering and Professor of Jet Propulsion, Emeritus, passed away on August 11, 2014, two months after the death of Ora Lee Marble, his wife of 71 years. Marble was one of the fathers of modern jet engines; his doctoral thesis included a method for calculating the three-dimensional airflow through rows of rotating blades. A jet engine is essentially two sets of blades on a common axle. A compressor at the front of the engine slows the incoming air and feeds it to the burner, and a turbine spinning in the hot gases downstream ejects the exhaust and drives the compressor. More broadly, Marble's methods apply to any fluid flowing along the axis of a fan, pump, turbine, or propeller.

Born in Cleveland, Ohio, on July 21, 1918, 15 years after the Wright brothers' first powered flight, Marble got interested in aviation in grade school. The Cleveland airfield was "a long streetcar ride away," he recalled in his Caltech oral history, and he "could wander into the hangars" unsupervised. He got his pilot's license before his driver's license.

Marble earned his BS in aeronautics in 1940 at the Case School of Applied Science (now Case Western Reserve University), "about a two-mile walk from home." For his master's degree in 1942, he built a fan designed to measure the surface pressure along a blade as it cut through the air. Holes in the blade led to a set of pressure gauges; the trick, he noted, was inventing the "slip seal" at the fan's hub that kept the holes and their gauges connected. He brought the data with him to Caltech, where it eventually became the basis for his PhD work.

But first, Marble helped fight World War II from the Cleveland airport, joining the National Advisory Committee for Aeronautics' Aircraft Engine Research Lab (now NASA's John H. Glenn Research Center at Lewis Field). Marble led the team troubleshooting the B-29 Superfortress, capable of flying thousands of miles at 30,000 feet with 10 tons of bombs. The "Superfort" was the biggest, heaviest plane of the war and its four engines often overheated; a significant number were ditched in the Pacific after engine fires. Several alterations to the airflow maximized the engine cooling, and the B-29 would remain in service into the 1960s.

On receiving his doctorate from Caltech in 1948, Marble was hired as an assistant professor by Tsien Hsue-shen (PhD '39), the Goddard Professor of Jet Propulsion. Tsien assigned him to develop a set of courses in this new field, which blended chemistry, gas dynamics, and materials science.

Tsien also gave Marble a half-time appointment at Caltech's Jet Propulsion Laboratory (JPL), which in the pre-NASA era really was studying jet propulsion, developing missiles under contract with the army. Tsien and his fellow members of the "suicide squad" had founded JPL in the wide-open scrublands of the upper Arroyo Seco in the 1930s after a string of accidents and explosions had gotten them evicted from the campus aeronautics lab. By the late 1940s, JPL had grown into an unrivaled set of testing facilities sprawled across some 60 acres.

Marble was put in charge of the group trying to build a workable ramjet—a turbine-less supersonic engine that compresses air by "ramming" it into an inlet that rapidly slows it to subsonic speeds. An ordinary turbojet's ignition source sits in a flame holder, or "can," mounted just behind the compressor. Like a rock in a river, this obstruction creates an eddy in its wake where hot, slow-moving gas gets trapped. This region of relative calm nurtured a stable flame. In a ramjet, however, a momentary tongue of flame would blow out the back of the engine just before it quit.

Marble attacked the problem by repurposing the ramjet lab for combustion research, leading to a string of breakthroughs in the mid-1950s. First, he and graduate student Tom Adamson (MS '50, PhD '54) mathematically analyzed the contact zone between the fuel and the wake. The fuel diffuses across this mixing layer and ignites on contact with the wake, replenishing the eddy's hot gas. By assuming that the mixing layer's gases flowed in a parallel, laminar fashion, Marble and Adamson were able to predict how far downstream the fuel would catch fire and how stable the flame would be. Says Adamson, "We didn't answer every question about combustion in laminar mixing, but we answered many of them." Studies of premixed ignition still refer to the "Marble-Adamson problem" as a paradigm.

High-speed "movies" of the flame confirmed the laminar ignition theory. The movies also showed why the flame blew out—as the airflow increased, the mixing layer suddenly turned turbulent. This dislodged the eddy, which promptly dissipated. The results were "scalable," meaning that they could be applied to any combination of fuel and hardware to find a flame-holder diameter and airstream velocity that would guarantee a steady burn.

Other movies demystified the mechanism behind a type of catastrophic engine failure whose early stages were announced by a 160-decibel screech. These images revealed that the curling tendrils of burnt fuel entering the eddy conjured up opposing whirlpools in order to keep the flow's overall angular momentum in balance. This second set of whirlpools spread outward, and if they withdrew enough heat from the mixing layer, they would themselves ignite. A natural acoustic resonance in the engine could then amplify their thermal energy tenfold en route to the walls. "My desk was 600 feet away," Adamson says. "When the motor began to screech, things shook so hard I couldn't write."

Marble's group also figured out what makes a compressors stall, which happens when its rotating blades lose their "bite." (In a bad stall, the high-pressure surge of air escaping backward through the compressor can do enough damage to bring down an airplane.) Howard Emmons at Harvard had found that an individual blade stalled when it entered a cell of reduced pressure that separated the airflow from the blade, and that these cells leapt from blade to blade; think of the slats of a Venetian blind rippling up and down in a breeze. Marble developed a two-dimensional model of the ripple's essential features—a neat complement to his PhD work on unstalled flow.

Meanwhile, the Chinese-born Tsien had fallen victim to the Red Scare. His top-secret clearance was revoked in the autumn of 1950. For the next five years the Immigration and Naturalization Service forbade him from leaving Caltech's environs. He was unable to enter JPL, or to participate in classified research on campus—in effect, barred from aeronautics altogether. When the Tsiens were evicted from the house they rented, Marble found them another; when they were evicted from that one as well, the Marbles took them in. (Ironically, after being deported in 1955, the embittered Tsien did join the Communist Party and led China into the space age.)

Marble returned to campus full-time in 1959 and began studying multiphase gas dynamics, in which a gas carries tiny particles—in this case, motes of aluminum oxide, routinely added to solid rocket fuels to make them burn hotter. The grains moved more slowly than the gas and their mass affected its flow, causing the rockets to underperform. Marble helped design the nozzle for the solid-fuel Minuteman intercontinental ballistic missile in the early 1960s, but it took most of the decade to work out a complete mathematical treatment of dusty flows.

Marble spent the '70s studying various sources of jet-engine noise before returning to combustion research. Caltech professors Anatol Roshko (MS '47, PhD '52) and Garry Brown had shown in the early '70s that a turbulent shear flow's swirls retained their identities for considerable distances downstream, stretching the mixing layer and wrapping it around itself. Marble and graduate student Ann Karagozian (PhD '82) set about studying how diffusion-driven flames interacted with these vortices—"a very fundamental problem," says Karagozian. "Frank pioneered the coherent-flame model of turbulent combustion, and researchers still use 'flamelet models' in very complicated turbulent combustion simulations."

In addition to his research accomplishments, Marble was legendary for his teaching prowess—and his penchant for 8:00 a.m. lectures delivered "with breathtaking clarity and almost without notes," Karagozian says. "It was tough getting up early for them, but the lectures were incredibly stimulating and rigorous."

Marble's 60-odd graduate students included a who's-who of aerospace engineers as well as Benoit Mandelbrot (Eng '49), the father of fractal geometry. The Frank and Ora Lee Marble Professorship and a graduate fellowship have been established by his students and friends to honor his impact as a mentor as well as a scientist.

Marble was an elected member of both the National Academy of Engineering and the National Academy of Sciences, a rare distinction, and a fellow of the American Institute of Aeronautics and Astronautics (AIAA). His other honors included the AIAA's Propellants and Combustion Award and the Daniel Guggenheim Medal, often regarded as the Nobel Prize of aeronautics.

Marble is survived by his son, Stephen; his daughter-in-law, Cheryl; two grandchildren and one great-grandson. Marble's daughter, Patricia, died in 1996.

A memorial service is planned for Saturday, October 4. 

Douglas Smith
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Ceramics Don't Have To Be Brittle

Caltech Materials Scientists Are Creating Materials By Design

Imagine a balloon that could float without using any lighter-than-air gas. Instead, it could simply have all of its air sucked out while maintaining its filled shape. Such a vacuum balloon, which could help ease the world's current shortage of helium, can only be made if a new material existed that was strong enough to sustain the pressure generated by forcing out all that air while still being lightweight and flexible.

Caltech materials scientist Julia Greer and her colleagues are on the path to developing such a material and many others that possess unheard-of combinations of properties. For example, they might create a material that is thermally insulating but also extremely lightweight, or one that is simultaneously strong, lightweight, and nonbreakable—properties that are generally thought to be mutually exclusive.

Greer's team has developed a method for constructing new structural materials by taking advantage of the unusual properties that solids can have at the nanometer scale, where features are measured in billionths of meters. In a paper published in the September 12 issue of the journal Science, the Caltech researchers explain how they used the method to produce a ceramic (e.g., a piece of chalk or a brick) that contains about 99.9 percent air yet is incredibly strong, and that can recover its original shape after being smashed by more than 50 percent.

"Ceramics have always been thought to be heavy and brittle," says Greer, a professor of materials science and mechanics in the Division of Engineering and Applied Science at Caltech. "We're showing that in fact, they don't have to be either. This very clearly demonstrates that if you use the concept of the nanoscale to create structures and then use those nanostructures like LEGO to construct larger materials, you can obtain nearly any set of properties you want. You can create materials by design."

The researchers use a direct laser writing method called two-photon lithography to "write" a three-dimensional pattern in a polymer by allowing a laser beam to crosslink and harden the polymer wherever it is focused. The parts of the polymer that were exposed to the laser remain intact while the rest is dissolved away, revealing a three-dimensional scaffold. That structure can then be coated with a thin layer of just about any kind of material—a metal, an alloy, a glass, a semiconductor, etc. Then the researchers use another method to etch out the polymer from within the structure, leaving a hollow architecture.

The applications of this technique are practically limitless, Greer says. Since pretty much any material can be deposited on the scaffolds, the method could be particularly useful for applications in optics, energy efficiency, and biomedicine. For example, it could be used to reproduce complex structures such as bone, producing a scaffold out of biocompatible materials on which cells could proliferate.

In the latest work, Greer and her students used the technique to produce what they call three-dimensional nanolattices that are formed by a repeating nanoscale pattern. After the patterning step, they coated the polymer scaffold with a ceramic called alumina (i.e., aluminum oxide), producing hollow-tube alumina structures with walls ranging in thickness from 5 to 60 nanometers and tubes from 450 to 1,380 nanometers in diameter.

Greer's team next wanted to test the mechanical properties of the various nanolattices they created. Using two different devices for poking and prodding materials on the nanoscale, they squished, stretched, and otherwise tried to deform the samples to see how they held up.

They found that the alumina structures with a wall thickness of 50 nanometers and a tube diameter of about 1 micron shattered when compressed. That was not surprising given that ceramics, especially those that are porous, are brittle. However, compressing lattices with a lower ratio of wall thickness to tube diameter—where the wall thickness was only 10 nanometers—produced a very different result.

"You deform it, and all of a sudden, it springs back," Greer says. "In some cases, we were able to deform these samples by as much as 85 percent, and they could still recover."

To understand why, consider that most brittle materials such as ceramics, silicon, and glass shatter because they are filled with flaws—imperfections such as small voids and inclusions. The more perfect the material, the less likely you are to find a weak spot where it will fail. Therefore, the researchers hypothesize, when you reduce these structures down to the point where individual walls are only 10 nanometers thick, both the number of flaws and the size of any flaws are kept to a minimum, making the whole structure much less likely to fail.

"One of the benefits of using nanolattices is that you significantly improve the quality of the material because you're using such small dimensions," Greer says. "It's basically as close to an ideal material as you can get, and you get the added benefit of needing only a very small amount of material in making them."

The Greer lab is now aggressively pursuing various ways of scaling up the production of these so-called meta-materials.

The lead author on the paper, "Strong, Lightweight and Recoverable Three-Dimensional Ceramic Nanolattices," is Lucas R. Meza, a graduate student in Greer's lab. Satyajit Das, who was a visiting student researcher at Caltech, is also a coauthor. The work was supported by funding from the Defense Advanced Research Projects Agency and the Institute for Collaborative Biotechnologies. Greer is also on the board of directors of the Kavli Nanoscience Institute at Caltech.

Kimm Fesenmaier
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Wednesday, September 24, 2014

A chance to meet Pasadena Unified School District Leadership

Measuring Earthquake Shaking with the Community Seismic Network

In 2011, the Community Seismic Network (CSN) began taking data from small, inexpensive accelerometers in the greater Pasadena area. Able to measure both weak and strong ground movement along three axes, these accelerometers promise to provide very high-resolution data of shaking produced by seismic activity in the region. "We have quite a large deployment of these accelerometers, about 400 sensors now, in people's homes but also in schools and businesses, and in some high-rise buildings downtown," says Julian Bunn, principal computational scientist for Caltech's Center for Advanced Computing Research. "We run client software on each sensor that sends data up into Google's cloud. From there we can analyze the data from all these sensors."

The CSN is the brainchild of Professor of Geophysics Rob Clayton, Professor of Engineering Seismology Tom Heaton, and Simon Ramo Professor of Computer Science, Emeritus, K. Mani Chandy, and a collaboration among Caltech's seismology, earthquake engineering, and computer science departments. It has successfully detected the many earthquakes that have occurred since its establishment. In addition, the CSN currently assists in damage assessment by generating maps of peak ground acceleration before accurate measurements of the earthquake epicenter or magnitude are known.

However, the CSN could provide further assistance in damage assessment if it were also able to produce an immediate estimation of the magnitude. "Right now we only detect an event," says Bunn. "We don't estimate the magnitude." This is where Caltech junior Kevin Li comes in. Li has been spending his 10-week Summer Undergraduate Research Fellowship (SURF) trying to develop a machine-learning system that can accurately estimate the magnitude of an earthquake within seconds of its detection.

Of course, the USGS already accurately measures earthquake magnitudes, but it does so by means of highly sophisticated—and expensive—seismometers that are located several miles apart from one another. Post-quake "ShakeMaps" are then constructed by extrapolating from this data to estimate shaking between seismometer stations. The problem, as recent quakes in California have shown, is that shaking can vary widely even from block to block—as can damage and potential injuries. The CSN proposes to capture this variation and provide an important resource for first responders during major earthquakes, pinpointing areas likely to have the most damage. Should this pilot study prove fruitful, says Bunn, it could "provide better hazard mitigation in parts of the world where they can't afford these very expensive installations."

"Seismic networks like the USGS use really fine sensors," explains Li. "However, the CSN sensors sacrifice fine measurement precision for low-cost efficiency. The sensors record particularly noisy data, far noisier than what the USGS system is used to. As a result, we cannot just adopt the algorithms from USGS. We need to develop our own system."

So far, says Li, the work is going well. "I'm currently still in week nine of my 10 weeks, but I have a system that seems like it can give a magnitude estimate that is within 1 unit of magnitude. For instance, if the estimation is 5.4, then the real magnitude should be somewhere between 4.4 and 6.4. If we can get to better precision than that, even better."

Li notes that his system has so far only been evaluated using USGS magnitudes for previous seismic events over the past two years. "I have yet to test it on a new event. Perhaps I can test it on the data from the recent earthquake in Napa once Caltech has finished processing it."

CSN is supported by funding from the Gordon and Betty Moore Foundation.

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Measuring Earthquake Shaking
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Wednesday, September 10, 2014
Avery Dining Hall – Avery House

RESCHEDULED to Sept 24th: A chance to meet Pasadena Unified School District Leadership

Atwater to Receive Applied Physics Prize

Harry Atwater, Caltech's Howard Hughes Professor of Applied Physics and Materials Science in the Division of Engineering and Applied Science, and director of the Resnick Sustainability Institute, has been named a recipient of this year's Julius Springer Prize for Applied Physics.

The annual prize, awarded by the editors in chief of the research journals Applied Physics A—Materials Science & Processing and Applied Physics B—Lasers and Optics, recognizes researchers who have made "an outstanding and innovative contribution" to the field of applied physics.

Atwater, who is also director of the Department of Energy's Energy Frontier Research Center on Light-Material Interactions in Energy Conversion at Caltech, and the editor in chief of the journal ACS Photonics, shares the award with Albert Polman of AMOLF, a research laboratory of the Foundation for Fundamental Research on Matter (FOM) in the Netherlands.

The two longtime collaborators were cited for their key contributions to the research area of nanophotonics, the science of light at the nanoscale, and, in particular, their development of metallic nanostructures that help to control light at these vanishingly small scales. "Atwater and Polman have demonstrated how light can be more efficiently absorbed and trapped in solar cells by integrating nanostructures in the solar cell," according to the award announcement. "This enables the fabrication of ultrathin solar cells that can be made at reduced costs, as well as new solar cell architectures with increased efficiency."

The award, which comes with a cash prize of $5,000, will be presented on September 1 at the Muziekgebouw in Amsterdam during the Julius Springer Forum on Applied Physics 2014.

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Programmed to Fold: RNA Origami

Researchers from Aarhus University in Denmark and Caltech have developed a new method for organizing molecules on the nanoscale. Inspired by techniques used for folding DNA origami—first invented by Paul Rothemund, a senior research associate in computation and neural systems in the Division of Engineering and Applied Science at Caltech—the team, which includes Rothemund, has fabricated complicated shapes from DNA's close chemical cousin, RNA.

Unlike DNA origami, whose components are chemically synthesized and then folded in an artificial heating and cooling process, RNA origami are synthesized enzymatically and fold up as they are being synthesized, which takes place under more natural conditions compatible with living cells. These features of RNA origami may allow designer RNA structures to be grown within living cells, where they might be used to organize cellular enzymes into biochemical factories.

"The parts for a DNA origami cannot easily be written into the genome of an organism. An RNA origami, on the other hand, can be represented as a DNA gene, which in cells is transcribed into RNA by a protein machine called RNA polymerase," explains Rothemund.

So far, the researchers have demonstrated their method by designing RNA molecules that fold into rectangles and then further assemble themselves into larger honeycomb patterns. This approach was taken to make the shapes recognizable using an atomic force microscope, but many other shapes should be realizable.

A paper describing the research appears in the August 15 issue of the journal Science.

"What is unique about the method is that the folding recipe is encoded into the molecule itself, through its sequence." explains first author Cody Geary, a postdoctoral scholar at Aarhus University.

In other words, the sequence of the RNAs defines both the final shape, and the order in which different parts of the shape fold. The particular RNA sequences that were folded in the experiment were designed using software called NUPACK, created in the laboratory of Caltech professor Niles Pierce. Both the Rothemund and Pierce labs are funded by a National Science Foundation Molecular Programming Project (MPP) Expeditions in Computing grant.

"Our latest research is an excellent example of how tools developed by one part of the MPP are being used by another," says Rothemund.

"RNA has a richer structural and functional repertoire than DNA, and so I am especially interested in how complex biological motifs with special 3-D geometries or protein-binding regions can be added to the basic architecture of RNA origami," says Geary, who completed his BS in chemistry at Caltech in 2003.

The project began with an extended visit by Geary and corresponding author Ebbe Andersen, also from Aarhus University, to Rothemund's Caltech lab.

"RNA origami is still in its infancy," says Rothemund. "Nevertheless, I believe that RNA origami, because of their potential to be manufactured by cells, and because of the extra functionality possible with RNA, will have at least as big an impact as DNA origami."

Rothemund (BS '94) reported the original method for DNA origami in 2006 in the journal Nature. Since then, the work has been cited over 2,000 times and DNA origami have been made in over 50 labs worldwide for potential applications such as drug delivery vehicles and molecular computing.

"The payoff is that unlike DNA origami, which are expensive and have to be made outside of cells, RNA origami should be able to be grown cheaply in large quantities, simply by growing bacteria with genes for them," he adds. "Genes and bacteria cost essentially nothing to share, and so RNA origami will be easily exchanged between scientists."


Katie Neith
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Frank E. Marble

Frank E. Marble, the Richard L. and Dorothy M. Hayman Professor of Mechanical Engineering and Professor of Jet Propulsion, Emeritus, at Caltech, passed away on August 11. He was 96.
Marble received his bachelor of science degree in 1940 and his master's degree in 1942, both from the Case Institute of Technology. He then came to Caltech and earned an engineer's degree in 1947 and a PhD in 1948, with Professor Theodore von Kármán as his advisor. He was hired at Caltech in 1948 as an instructor in aeronautics, became assistant professor of jet propulsion and mechanical engineering in 1949, associate professor in 1953, professor in 1957, and was named Hayman Professor of Mechanical Engineering and Professor of Jet Propulsion in 1980. He retired in 1989. 
Marble made major contributions to aerodynamics, combustion, and propulsion, specifically the research and development of gas turbines and rockets. He also was responsible for the training of several generations of scientists in the field of aeronautics. 
A member of both the National Academy of Engineering and the National Academy of Sciences, Marble received many honors for his contributions, including the 1999 Daniel Guggenheim Medal, awarded by the American Institute of Aeronautics and Astronautics (AIAA), and the AIAA Combustion Award. 
Marble was predeceased by Ora Lee, his wife of seven decades. 
A full obituary will be posted at a later date.
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Study of Aerosols Stands to Improve Climate Models

Aerosols, tiny particles in the atmosphere, play a significant role in Earth's climate, scattering and absorbing incoming sunlight and affecting the formation and properties of clouds. Currently, the effect that these aerosols have on clouds represents the largest uncertainty among all influences on climate change.

But now researchers from Caltech and the Jet Propulsion Laboratory have provided a global observational study of the effect that changes in aerosol levels have on low-level marine clouds—the clouds that have the largest impact on the amount of incoming sunlight that Earth reflects back into space. The findings appear in the advance online version of the journal Nature Geoscience.

Changes in aerosol levels have two main effects—they alter the amount of clouds in the atmosphere and they change the internal properties of those clouds. Using measurements from several of NASA's Earth-monitoring satellites from August 2006 through April 2011, the researchers quantified for the first time these two effects from 7.3 million individual data points.

"If you combine these two effects, you get an aerosol influence almost twice that estimated in the latest report from the Intergovernmental Panel on Climate Change," says John Seinfeld, the Louis E. Nohl Professor and professor of chemical engineering at Caltech. "These results offer unique guidance on how warm cloud processes should be incorporated in climate models with changing aerosol levels."

The lead author of the paper, "Satellite-based estimate of global aerosol-cloud radiative forcing by marine warm clouds," is Yi-Chun Chen (Ph.D. '13), a NASA postdoctoral fellow at JPL. Additional coauthors are Matthew W. Christensen of JPL and Colorado State University and Graeme L. Stephens, director of the Center for Climate Sciences at JPL. The work was supported by funding from NASA and the Office of Naval Research.

Kimm Fesenmaier
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