Caltech Students Work on Proposed Space Mission for Final Project

Forget problem sets and exams. For their homework and final assignments, students in Caltech's Aerospace Engineering course (Ae105) work on a proposed space mission. For the past few years, students in the class have helped design, prototype, and test various pieces of AAReST, a space-telescope demonstration mission currently under development.

"It's really different from all of our other classes," says graduate student Manan Arya, who took the course this year. "You're actually doing work that's going to go into space. It's really exciting."

Space-based optical telescopes with large primary mirrors or lenses hold promise for expanding human knowledge of Earth and the universe. Larger primary optics allow telescopes to gather more light, and therefore, to peer farther into the cosmos. Currently, the push is to develop space-based telescopes with primary optics larger than 10 meters in diameter (in comparison, the Hubble Space Telescope's primary mirror has a diameter of 2.4 meters). At the moment, though, the size of the mirrors is limited by the diameter of their launch vehicles. One way around the problem? Launch many small, independent spacecraft, each outfitted with its own mirror. Once in orbit, these craft would reconfigure themselves into a single large, segmented aperture.

AAReST (Autonomous Assembly of a Reconfigurable Space Telescope) is a low-cost mission intended to demonstrate the feasibility of this concept. Now in the pre-mission phase, AAReST has a projected launch date of 2015.

Seizing the opportunity to give students some hands-on experience, Sergio Pellegrino, Caltech's Joyce and Kent Kresa Professor of Aeronautics and professor of civil engineering, who is also a senior research scientist at the Jet Propulsion Laboratory (JPL), worked the mission into the Ae105 curriculum. His partners in this effort are JPL engineers Behcet Acikmese, Greg Davis, and Yunjin Kim. The year-long course they devised is fairly traditional for the first term and a half, and then switches to a project-based course to fill out the year.

Recently, this year's students presented the results of their final projects, which involved everything from designing and testing a new method for deploying the spacecraft boom to developing an algorithm to correct the telescope's focusing errors. Prior to the presentations, Pellegrino praised the students for their hard work and creativity. "They have moved the mission forward by a huge step this year, and I thank them for this," he said.

The efforts of the Ae105 students provide a burst of energy for the team that works on AAReST during the rest of the year, Pellegrino says. In past years, the class devised a completely new configuration for the spacecraft; this year, they refined it. "The initial concept has been transformed by the students' input," Pellegrino says.

In addition to being advised by the instructors, the students are mentored by several former Ae105 students and other JPL employees. One of Manan's mentors was retired JPLer Jim Breckinridge, who managed the team that built the camera that corrected the Hubble Space Telescope's originally flawed vision.

"When somebody has that much experience, and they're right next to you on the experimental setup, helping you out one-on-one—that's a rare opportunity," Manan says. "And it's a lot of fun."

The AAReST mission is a collaborative effort between Caltech, JPL, and the University of Surrey, in England. The pre-mission's project manager is JPL's John Baker. The Ae105 class has received funding from the Keck Institute for Space Studies, Caltech's Division of Engineering and Applied Science, and the Innovation in Education Fund, which was made possible in part by the Caltech Associates.

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SEM Honors Rosakis

The Society for Experimental Mechanics (SEM) has selected Ares Rosakis as the recipient of the P.S. Theocaris Award. Rosakis is Caltech's Theodore von Karman Professor of Aeronautics, professor of mechanical engineering, and chair of the Division of Engineering and Applied Science.

The award is intended "to recognize a senior individual for distinguished, innovative and outstanding work in optical methods and experimental mechanics."

In a letter to Rosakis, the chair of the SEM Honors Committee, Kristin Zimmerman, wrote, "Your selection is a well-deserved public statement by your peers of the quality and practicality of your professional contributions."

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The Physics of Going Viral

Caltech researchers measure the rate of DNA transfer from viruses to bacteria

PASADENA, Calif.—Researchers at the California Institute of Technology (Caltech) have been able, for the first time, to watch viruses infecting individual bacteria by transferring their DNA, and to measure the rate at which that transfer occurs. Shedding light on the early stages of infection by this type of virus—a bacteriophage—the scientists have determined that it is the cells targeted for infection, rather than the amount of genetic material within the viruses themselves, that dictate how quickly the bacteriophage's DNA is transferred.

"The beauty of our experiment is we were able to watch individual viruses infecting individual bacteria,"says Rob Phillips, the Fred and Nancy Morris Professor of Biophysics and Biology at Caltech and the principal investigator on the new study. "Other studies of the rate of infection have involved bulk measurements. With our methods, you can actually watch as a virus shoots out its DNA."

The new methods and results are described in a paper titled "A Single-Molecule Hershey–Chase Experiment," which will appear in the July 24 issue of the journal Current Biology and currently appears online. The lead authors of that paper, David Van Valen and David Wu, completed the work while graduate students in Phillips's group.

In the well-known 1952 Hershey-Chase experiment, Alfred Hershey and Martha Chase of the Carnegie Institution of Washington in Cold Spring Harbor convincingly confirmed earlier claims that DNA—and not protein—was the genetic material in cells. To prove this, the researchers used bacteriophages, which are able to infect bacteria using heads of tightly bundled DNA coated in a protein shell. Hershey and Chase radiolabeled sulfur, contained in the protein shell but not in the DNA, and phosphorous, found in the DNA but not in the protein shell. Then they let the bacteriophages infect the bacterial cells. When they isolated the cells and analyzed their contents, they found that only the radioactive phosphorous had made its way into the bacteria, proving that DNA is indeed the genetic material. The results also showed that, unlike the viruses that infect humans, bacteriophages transmit only their genetic information into their bacterial targets, leaving their "bodies" behind.

"This led, right from the get-go, to people wondering about the mechanism—about how the DNA gets out of the virus and into the infected cell," Phillips says. Several hypotheses have focused on the fact that the DNA in the virus is under a tremendous amount of pressure. Indeed, previous work has shown that the genetic material is under more pressure within its protein shell than champagne experiences in a corked bottle. After all, as Phillips says, "There are 16 microns of DNA inside of a tiny 0.05 micron-sized shell. It's like taking 500 meters of cable from the Golden Gate Bridge and putting it in the back of a FedEx truck." 

Phillips's group wanted to find out whether that pressure plays a dominant role in transferring the DNA. Instead, he says, "What we discovered is that the thing that mattered most was not the pressure in the bacteriophage, but how much DNA was in the bacterial cell."

The researchers used a fluorescent dye to stain the DNA of two mutants of a bacteriophage known as lambda bacteriophage—one with a short genome and one with a longer genome—while that DNA was still inside the phage. Using a fluorescence microscope, they traced the glowing dye to see when and over what time period the viral DNA transferred from each phage into an E. coli bacterium. The mean ejection time was about five minutes, though that time varied considerably.

This was markedly different from what the group had seen previously when they ran a similar experiment in a test tube. In that earlier setup, they had essentially tricked the bacteriophages into ejecting their DNA into solution—a task that the phages completed in less than 10 seconds. In that case, once the phage with the longer genome had released enough DNA to make what remained inside the phage equal in length to the shorter genome, the two phages ejected DNA at the same rate. Therefore, Phillips's team reasoned, it was the amount of DNA in the phage that determined how quickly the DNA was transferred.

But Phillips says, "What was true in the test tube is not true in the cell." E. coli cells contain roughly 3 million proteins within a box that is roughly one micron on each side. Less than a hundredth of a micron separates each protein from its neighbors. "There's no room for anything else," Phillips says. "These cells are really crowded." 

And so, when the bacteriophages try to inject their DNA into the cells, the factor that limits the rate of transfer is how jam-packed those cells are. "In this case," Phillips says, "it had more to do with the recipient, and less to do with the pressure that had built up inside the phage."

Looking toward the future, Phillips is interested in using the methods he and his team have developed to study different types of bacteriophages. He also wants to investigate various molecules that could be helping to actively pull the viral DNA into the cells. In the case of a bacteriophage called T7, for instance, previous work has shown that the host cell actually grabs onto the DNA and begins making copies of its genes before the virus has even delivered all the DNA into the cell. "We're curious whether that kind of mechanism is in play with the lambda bacteriophage," Phillips says.

The current findings have implications for the larger question of how biomolecules like DNA and proteins cross membranes in general, and not just into bacteria. Cells are full of membranes that divide them into separate compartments and that separate entire cells from the rest of the world. Much of the business of cellular life involves getting molecules across those barriers. "This process that we've been studying is one of the most elementary examples of what you could call polymer translocation or getting macromolecules across membranes," Phillips says. "We are starting to figure out the physics behind that process."

In addition to Phillips, Van Valen, and Wu, the other authors on the Current Biology paper are graduate student Yi-Ju Chen; Hannah Tuson of the University of Wisconsin at Madison; and Paul Wiggins of the University of Washington. Van Valen is currently a medical student at UCLA's David Geffen School of Medicine, and Wu is an intern at the University of Chicago. The work was supported by funding from the National Science Foundation, a National Institutes of Health Medical Scientist Training Program fellowship, a Fannie and John Hertz Yaser Abu-Mostafa Graduate Fellowship, and an NIH Director's Pioneer Award.

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Seeing Inside Tissue

Caltech researchers develop technique to focus light inside biological tissue

PASADENA, Calif.—Imagine if doctors could perform surgery without ever having to cut through your skin. Or if they could diagnose cancer by seeing tumors inside the body with a procedure that is as simple as an ultrasound. Thanks to a technique developed by engineers at the California Institute of Technology (Caltech), all of that may be possible in the not-so-distant future.

The new method enables researchers to focus light efficiently inside biological tissue. While the previous limit for how deep light could be focused was only about one millimeter, the Caltech team is now able to reach two and a half millimeters. And, in principle, their technique could focus light as much as a few inches into tissue. The technique is used much like a flashlight shining on the body's interior, and may eventually provide researchers and doctors with a host of possible biomedical applications, such as a less invasive way of diagnosing and treating diseases.

If you crank up the power of light, you might even be able to do away with a traditional scalpel. "It enables the possibilities of doing incision-less surgery," says Changhuei Yang, a professor of electrical engineering and bioengineering at Caltech and a senior author on the new study. "By generating a tight laser-focus spot deep in tissue, we can potentially use that as a laser scalpel that leaves the skin unharmed."

Ying Min Wang, a graduate student in electrical engineering, and Benjamin Judkewitz, a postdoctoral scholar, are the lead authors on the paper, which was published in the June 26 issue of the journal Nature Communications.

The new work builds on a previous technique that Yang and his colleagues developed to see through a layer of biological tissue, which is opaque because it scatters light. In the previous work, the researchers shined light through the tissue and then recorded the resulting scattered light on a holographic plate. The recording contained all the information about how the light beam scattered, zigzagging through the tissue. By playing the recording in reverse, the researchers were able to essentially send the light back through to the other side of the tissue, retracing its path to the original source. In this way, they could send light through a layer of tissue without the blurring effect of scattering.

But to make images of what is inside tissue—to get a picture of cells or molecules that are embedded inside, say, a muscle—the researchers would have to be able to focus a light beam into the tissue. "For biologists, it's most important to know what's happening inside the tissue," Wang says.

To focus light into tissue, the researchers expanded on the recent work of Lihong Wang's group at Washington University in St. Louis (WUSTL); they had developed a method to focus light using the high-frequency vibrations of ultrasound. The WUSTL group took advantage of two properties of ultrasound. First, the high-frequency sound waves are not scattered by tissue, which is why it is great for taking images of fetuses in utero. Second, ultrasonic vibrations interact with light in such a way that they shift the light's frequency ever so slightly. As a result of this so-called acousto-optic effect, any light that has interacted with ultrasound changes into a slightly different color.

In both the WUSTL and Caltech experiments, the teams focused ultrasound waves into a small region inside a tissue sample. They then shined light into the sample, which, in turn, scattered the light. Because of the acousto-optic effect, any of the scattered light that passes through the region with the focused ultrasound will change to a slightly different color. The researchers can pick out this color-shifted light and record it. By employing the same playback technique as in the earlier Caltech work, they then send the light back, having only the color-shifted bits retrace their path to the small region where the ultrasound was focused—which means that the light itself is focused on that area, allowing an image to be created. The researchers can control where they want to focus the light simply by moving the ultrasound focus.

The WUSTL experiment was limited, however, because only a very small amount of light could be focused. The Caltech engineers' new method, on the other hand, allows them to fire a beam of light with as much power as they want—which is essential for potential applications. 

The team demonstrated how the new method could be used with fluorescence imaging—a powerful technique used in a wide range of biological and biomedical research. The researchers embedded a patch of gel with a fluorescent pattern that spelled out "CIT" inside a tissue sample. Then, they scanned the sample with focused light beams. The focused light hit and excited the fluorescent pattern, resulting in the glowing letters "CIT" emanating from inside the tissue. The team also demonstrated their technique by taking images of tumors tagged with fluorescent dyes.

"This demonstration that we can focus significant optical power deep within tissues opens up significant possibilities in optical imaging," Yang says. By tagging cells or molecules that are markers for disease with fluorescent dyes, doctors can use this technique to make diagnoses noninvasively, much as if they were doing an ultrasound procedure.

Doctors might also use this process to treat cancer with photodynamic therapy. In this procedure, a drug that contains light-sensitive, cancer-killing compounds is injected into a patient. Cancer cells absorb those compounds preferentially, so that the compounds kill the cells when light shines on them. Photodynamic therapy is now only used at tissue surfaces, because of the way light is easily scattered. The new technique should allow doctors to reach cancer cells deeper inside tissue.

The team has been able to more than double the current limit for how far light can be focused into tissue. With future improvements on the optoelectronic hardware used to record and play back light, the engineers say, they may be able to reach 10 centimeters (almost 4 inches)—the depth limit of ultrasound—within a few years.

Still, the researchers say, their demonstration shows they have overcome the main conceptual hurdle for effectively focusing light deep inside tissue. "This is a big breakthrough, and we're excited about the potential," Judkewitz says. Adds Caltech's Wang, "It's a very new way to image into tissue, which could lead to a lot of promising applications."

The Nature Communications paper is titled "Deep-tissue focal fluorescence imaging with digitally time-reversed ultrasound-encoded light." In addition to Wang, Judkewitz, and Yang, the other author on the paper is Charles DiMarzio of Northeastern University. This work was supported by the National Institutes of Health, the Defense Advanced Research Projects Agency, the Sir Henry Wellcome Postdoctoral Fellowship from the Wellcome Trust, and the National Science Scholarship from the Agency for Science, Technology, and Research in Singapore.

Written by Marcus Woo

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Caltech Rover Team Wins Second Place in Robo-Ops Competition

After designing and building a four-wheeled remotely controlled rover, a team of Caltech students came away with second place in the RASC-AL Exploration Robo-Ops Competition at NASA's Johnson Space Center earlier this month. Despite a weather delay and some wayward sand, the robot operated as designed and managed to traverse different slopes and types of terrain in Johnson's Rock Yard, picking up four rock targets and an "alien" during the one-hour roving portion of the competition.

"All in all, the competition was a great success," says Justin Koch, the mobility system lead for the Caltech Rover Team and a mechanical engineering major who just completed his first year at Caltech. "Everyone on the team put in a lot of hours, and the quality of the rover demonstrated that it was time well spent." 

The Revolutionary Aerospace Systems Concepts Academic Linkage (RASC-AL) Exploration Robo-Ops Competition challenges teams of university students with the engineering task of designing and building a planetary rover prototype. Sponsored by NASA and organized by the National Institute of Aerospace, the competition gives students the opportunity to apply what they have learned in the classroom to a real-world problem. 

Caltech and seven other teams were selected as finalists based on written proposals submitted in December. Each team received $10,000 to build a rover and to send three team members and an advisor—in Caltech's case, that was Joel Burdick, professor of mechanical engineering and bioengineering—to the competition forum in Houston, which took place May 30 through June 1. The remaining members of each team stayed at their home institution to remotely operate their rovers. Thanks to a live video feed and the 4G network, the majority of Caltech's team was able to watch and control the rover's every move from "mission control" in the basement of Spalding Laboratory. 

During the roving portion of the competition, which accounted for 60 percent of the final score, each team had free rein on the course for one hour. The Caltech Rover Team started its run on May 31. They managed to pick up two colored target rocks in the sand pit, but ran into some problems with grains of sand getting into the joints of the rover arm's gripper. They used the five-minute "mulligan" every team gets to repair the rover, but the run was later interrupted by an approaching thunderstorm. 

They resumed their run the following day, navigating from the sand pit to the "lunar craters," where they found and picked up an "alien" toy. Before their hour of roving was up, they collected two additional rocks on the hill. 

"The roving portion of the competition at Houston was exciting to say the least," says rising junior Daniel Lo, the leader and organizer of Caltech's team and a physics and planetary science double major. "We encountered difficulties, things we did not expect, but I am really proud that as a team we persisted."

Out of a possible 60 points, the Caltech team received 39 for the roving portion of the competition. The first-place winners, Worcester Polytechnic University, earned the full 60 points, while the third-place team, from the University of Maryland, picked up six points. Teams were also judged on a technical paper, an oral poster presentation, and an education and public-outreach component.

For their second-place performance, the Caltech Rover Team received $4,000, which they plan to use on future robotics competitions. They also received a good-sportsmanship award for loaning their tools and duct tape to the University of Pennsylvania team when its rover broke down. Koch says the experience he gained was worth the time and effort. "I picked up a lot of hands-on knowledge that will be useful for future projects," he says.

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Caltech Graduating Senior Wins Multiple National Honors

When Caltech senior Arvind Kannan graduates on Friday, he will be one highly decorated Techer. During this academic year, the chemical engineering major racked up multiple honors that will support his graduate studies, including a Churchill Scholarship, a Hertz Foundation fellowship, and a National Science Foundation graduate research fellowship.

As one of only 14 new Churchill scholars, Kannan will spend the next academic year working on a Master of Philosophy in chemistry at the University of Cambridge. While there, he will work in the laboratory of Michele Vendruscolo, using computational methods to build a detailed structural model of a large protein complex called the 20S proteasome, which is involved in regulating processes ranging from gene expression to cell signaling. According to the Winston Churchill Foundation's website, the scholarship program "offers American citizens of exceptional ability and outstanding achievement the opportunity to pursue graduate studies in engineering, mathematics, or the sciences at Cambridge. 

When Kannan returns to the United States to complete a doctoral program at Stanford University, he will receive support from both the Fannie and John Hertz Foundation and the NSF Graduate Research Fellowship Program. These awards, Kannan says, will allow him to carry out an ambitious research project free from financial constraints. 

At Caltech, Kannan developed a passion for engineering proteins to do chemically useful things—like break down plant matter for use in biofuel production or speed up drug development. He has been working with Frances Arnold, the Dick and Barbara Dickinson Professor of Chemical Engineering, utilizing a technique called "directed evolution," which applies the principles of natural selection to molecules in the laboratory rather than animals or plants in nature.

"Arvind's brilliance and insatiable thirst for learning is matched by his commitment to studying and practicing science," says Arnold, who also described him as "well-rounded." Indeed, Kannan, has played the flute for eight years, has been singing Carnatic music—a type of South Indian classical music—since he was five years old, and is now a baritone in the Caltech Glee Club. "When not playing music, I love listening to it," he says. "I have also cultivated a passion for modern electronic dance music and enjoy participating in the major electronic music festivals of the L.A. area."

Of his time at Caltech, Kannan says he feels fortunate that the breadth of the curriculum and the diversity of opportunities for learning have prepared him so well for his future. He enjoys, for example, sitting at a lunch table with physics majors and biologists alike, and being able to join in conversations about both quantum field theory and cell signaling. "That experience, I think, has been really wonderful because science is an interdisciplinary, collaborative process," he says. "The more you know about other fields, the more it enriches both your own research and your appreciation for science as a whole."

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Caltech Rover Ready for Rock-Yard Competition in Houston

Later this week, a four-wheeled robot designed and built by Caltech undergraduate students will maneuver, apparently under its own guidance, through various challenges at the NASA Johnson Space Center Rock Yard in Houston. In actuality, the robot's every move will be under the control of a group of those students who will be located back on campus, in the basement of Spalding Laboratory.

The Caltech group, which is named simply the Caltech Rover Team, will be competing for glory and prizes in a contest whose name is quite a mouthful: the Revolutionary Aerospace Systems Concepts Academic Linkage (RASC-AL) Exploration Robo-Ops Competition. Sponsored by NASA and organized by the National Institute of Aerospace, the competition will take place during a three-day forum, beginning May 30. The challenge will test the ability of rovers from eight universities to navigate sand dunes, climb out of mock lunar craters, pick up rocks, and more—all while being tele-operated off-site.

"This has been an amazing experience," says sophomore Daniel Lo, a physics and planetary science double major and the leader and organizer of the Caltech team. "In the beginning, I couldn't have imagined that our rover would turn out this great."

Each of the eight university teams were chosen as finalists based on written proposals submitted in December, then given $10,000 to build their rover and to send three team members and an advisor to the competition in Houston. Joel Burdick, professor of mechanical engineering and bioengineering, and Issa Nesnas of the Jet Propulsion Laboratory are the Caltech team's advisors.

During a recent demonstration on campus attended by onlookers including Caltech president Jean-Lou Chameau, team member Harrison Miller stood at a picnic table and operated a sensored master arm made of acrylic; his movements were transmitted and copied by the rover's own robotic "slave" arm. "Oh, that's so buttery," Miller said, marveling at the master-slave arm-control system's latest improvements. He was able to lead the rover through a challenge known as the "Tower of Hanoi" problem, which requires picking up, moving, and setting down disks of various sizes and weights in a particular order.

In the actual competition, the rocks that the rover will have to pick up will be lighter and easier to grip than the disks used in the demonstration. "If we can do this, we'll be fine," said Russell Newman, the team's chief designer and a senior mechanical engineering major. In addition, the rover arm's six degrees of freedom should allow it to reach over and around obstacles to gain access to target rocks.

The Caltech robot uses a so-called rocker-bogie suspension system, in which the differential links, or "rockers," of the undercarriage keep the vehicle balanced. This type of system is used by NASA's Mars rovers to give them the ability to drive over relatively large rocks and varying terrain, without tilting drastically—and, possibly, toppling over. As it traverses the Rock Yard in Houston, the rover's eight cameras will feed visual information via Verizon's 4G network to the operating team located in Caltech's Jim Hall Design and Prototyping Lab; the network will also deliver the team's commands to the rover.

Each team, in addition to being judged based on their rover's performance in the challenge, will be evaluated on a final written report and on education and outreach efforts. Caltech's team, for example, has a website and Facebook and Twitter accounts for its rover and has shared the project with several groups of local school children. 

The competition in Houston will be streamed live on May 31 and June 1.

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Researchers Demonstrate Possible Primitive Mechanism of Chemical Info Self-Replication

PASADENA, Calif.— When scientists think about the replication of information in chemistry, they usually have in mind something akin to what happens in living organisms when DNA gets copied: a double-stranded molecule that contains sequence information makes two new copies of the molecule. But researchers at the California Institute of Technology (Caltech) have now shown that a different mechanism can also be used to copy sequence information.

In this alternate version, tiny DNA tile crystals consisting of many copies of a piece of information are first grown, then broken into a few pieces by mechanically-induced scission, or force. The new crystal bits contain all the information needed to keep copying the sequence. Each piece then begins to replicate its information and grow until broken apart again—without the help of enzymes, an essential ingredient in biological sequence replication. In some ways, the new system is reminiscent of Goethe's poem, The Sorcerer's Apprentice, in which the apprentice smashes a magic mop with an axe, producing many exact replicas of the sweeper, all programmed to do the same job.

"The genome-copying mechanism used by cells requires tight control between the separation of DNA strands and the copying process," explains study lead author Rebecca Schulman, an assistant professor at Johns Hopkins University who was a graduate student at Caltech when the research began.

"But no such coordination is required in the system we designed, which makes it simpler in many ways," she says. "This suggests that there may be other mechanisms of copying information that follow this method using chemistry that could be simpler than the process cells use. What we showed in the paper was a capacity to take a given chemical message—a sequence of 1s and 0s—and make more copies of that message through a new, designed self-replication process." 

The findings were reported in a recent issue of the Proceedings of the National Academy of Sciences (PNAS).

The idea that crystals can self-replicate was first presented by organic chemist and molecular biologist Graham Cairns-Smith in 1965. He proposed, as well, that such crystals might have been the first chemical self-replicators capable of Darwinian evolution. His theory was controversial at the time, and his ideas have never gained widespread support. But according to Erik Winfree, professor of computer science, computation and neural systems, and bioengineering at Caltech and senior author on the PNAS paper, this new research shows that Cairns-Smith's hypothesis on the origin of life is demonstrably more plausible than previously thought.

"Overall, we found that his principles and mechanisms are sound, and although we didn't experimentally demonstrate his theory all the way, self-replication via crystal growth and scission should be sufficient for Darwinian evolution," he says. "This is because DNA tile crystals can be programmed to process information during growth, allowing them to adapt to their environment. Our findings could even form the basis of novel molecular technologies for making complex self-replicating nanoscale objects."

Their new research found that it is possible to design a mechanism for copying chemical information very accurately without relying on biological enzymes to assemble and separate sequence copies. Instead, the researchers relied only on simple kinds of attachments—molecular binding and unbinding reactions that they designed—and mechanical forces.

Having shown that information can be made to chemically self-replicate, says Schulman, the question becomes, what kinds of messages can be copied in this way?

"Our theoretical work suggests that not just linear sequences but also patterns in two dimensions, similar to wallpaper patterns that repeat every so often, could also be replicated," she says.

The crystals used in the study simply copied information verbatim from layer to layer as they grew, which in itself is insufficient to kick-start a Darwinian evolutionary process.  But crystal growth that produces complex patterns resulting in 2- or 3-dimensional structures would, in this context, correspond to a rudimentary "genotype-phenotype" relationship, thereby enriching the Darwinian evolutionary process by introducing complex forms that would be subject to selective pressures, Winfree says. 

"Our findings show that there is a bewildering variety of imaginable ways that chemical systems could self-replicate and evolve," he says. "This really puts into question whether or not the way biology does things now is the only possible way that life could be organized on a molecular level."

The PNAS study, "Robust self-replication of combinatorial information via crystal growth and scission," was funded by the Miller Institute of Basic Science, the National Science Foundation, and a National Aeronautics and Space Administration astrobiology grant. Bernard Yurke, a Distinguished Research Fellow at Boise State in Idaho, is also a coauthor of the paper.

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Better, Stronger, Lighter Armor

What makes a piece of armor effective? Sure, it needs to be strong, and it should be lightweight. But what is it about a material's composition that gives it such properties? And can we develop materials that provide even better protection? With decades' worth of investment and preparation, Caltech engineers are particularly well equipped to address such questions as part of a new Army-funded program to improve protective gear and vehicles for soldiers.

The U.S. Army Research Laboratory recently announced that it would provide up to $90 million to a consortium of researchers—led by engineers at Johns Hopkins University's newly created Extreme Materials Institute—to investigate what happens to protective materials during intense impact. The collaboration includes engineers from national laboratories, private industry, and four universities—Caltech, Johns Hopkins, Rutgers University, and the University of Delaware. 

"Here at Caltech we have developed a very unique expertise and one-of-a-kind tools for trying to understand the behavior of structural materials across all scales," says Kaushik Bhattacharya, Caltech's lead in the army effort and the Howell N. Tyson, Sr., Professor of Mechanics and professor of materials science. "What the army recognizes is that such understanding can play a significant role in speeding up the process of developing new materials—a process that can take up to 20 years with standard methods."

Six engineers and applied scientists from Caltech's Division of Engineering and Applied Science will collaborate on the new project, focusing initially on magnesium alloys and boron carbide ceramics. Magnesium alloys—known by car buffs thanks to their incorporation into the wheels of fancy cars—are extremely strong, tough, and lightweight. But like most traditional alloys, they have been made empirically—that is, someone realized that by adding just so much aluminum, a little bit of zinc, and so on, they would wind up with a much stronger product than magnesium alone. No one has worked out the science explaining exactly why those small additions change the properties of the material, and so it's difficult to say if the alloys are performing at their peak or if the "recipe" could be improved.

"Right now we don't have a predictive model for designing advanced materials," Bhattacharya says. "We have some theories that guide us, but they really are not fully predictive." 

Developing the level of understanding needed to create such a predictive tool is an incredibly complex problem that requires engineers and applied scientists to tap into their knowledge of multiple disciplines. They must understand the mechanics across length scales from the subnanometer level—units smaller than billionths of meters—all the way to materials that can be measured in meters. They also need to understand how materials behave across timescales from femtoseconds—millionths of billionths of seconds—up to seconds, and at various temperatures and pressures.

"You have to somehow understand this complete hierarchy and how all of these pieces fit together," says Bhattacharya. "And you have to understand how all of the levels of hierarchy change during a high-velocity impact, such as when a bullet hits armor or a missile strikes a vehicle." 

Part of that requires understanding how the defects in a material will behave. It would be relatively easy to model a metal with a perfect crystal configuration—where all of its atoms line up to form an ideal lattice. But as materials scientists like to say, "Crystals are like people: it is the defects in them which tend to make them interesting." These defects, such as missing atoms and misalignments, can confer beneficial properties upon the material, giving it greater strength or ductility, for example.  But they also add a level of complexity; changing the placement of a single atom can have a large effect on the rest of the material.

Along with Bhattacharya, William Goddard III, Dennis Kochmann, and Michael Ortiz will work on the theory side of the problem, using a range of tools developed at Caltech over the last two decades to accurately model the behavior of materials from the subatomic level all the way to the scale of bulk materials.

On the experimental side, Guruswami Ravichandran will investigate how a material deforms, or changes shape, at different scales and temperatures when struck by a high-speed projectile. Meanwhile, Julia Greer will look at the deformation and mechanical properties of materials at the nanoscale.

"When you have a large chunk of a metal, such as magnesium, it deforms under certain known conditions. But if you make a very small sample of the same metal, it's going to have very different mechanical characteristics," says Greer. "So if you're planning on utilizing nanotechnology at all in a production application, you need to know first what your material's properties are at its various scales. We will provide that experimental data."

In addition to their participation in the army's extreme-materials project, Caltech engineers are working on several other programs focused on multiscale modeling of materials and the development of damage-tolerant materials. Ortiz is the principal investigator and director of Caltech's Predictive Science Academic Alliance Program Center, sponsored by the National Nuclear Security Administration, which focuses on the hypervelocity impacts of metallic projectiles. For his part, Ravichandran is heading up a new Center of Excellence funded by the Air Force Research Laboratory; it will look at the physics of what happens to materials ranging from sands to layered composites when they are suddenly struck by a powerful force and deform quickly.

"When you take these major projects together, you see that studying materials in very extreme conditions is an area where Caltech engineering really stand out," says Bhattacharya. "The tools we bring, on both the theoretical and experimental sides uniquely bridge deep fundamental principles with unprecedented application."

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Kimm Fesenmaier
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Caltech Researchers Gain Greater Insight into Earthquake Cycles

New dynamic computer model first to show full history of a fault segment

PASADENA, Calif.—For those who study earthquakes, one major challenge has been trying to understand all the physics of a fault—both during an earthquake and at times of "rest"—in order to know more about how a particular region may behave in the future. Now, researchers at the California Institute of Technology (Caltech) have developed the first computer model of an earthquake-producing fault segment that reproduces, in a single physical framework, the available observations of both the fault's seismic (fast) and aseismic (slow) behavior. 

"Our study describes a methodology to assimilate geologic, seismologic, and geodetic data surrounding a seismic fault to form a physical model of the cycle of earthquakes that has predictive power," says Sylvain Barbot, a postdoctoral scholar in geology at Caltech and lead author of the study.

A paper describing their model—the result of a Caltech Tectonics Observatory (TO) collaborative study by geologists and geophysicists from the Institute's Division of Geological and Planetary Sciences and engineers from the Division of Engineering and Applied Science—appears in the May 11 edition of the journal Science.

"Previous research has mostly either concentrated on the dynamic rupture that produces ground shaking or on the long periods between earthquakes, which are characterized by slow tectonic loading and associated slow motions—but not on both at the same time," explains study coauthor Nadia Lapusta, professor of mechanical engineering and geophysics at Caltech. Her research group developed the numerical methods used in making the new model. "In our study, we model the entire history of an earthquake-producing fault and the interaction between the fast and slow deformation phases."

Using previous observations and laboratory findings, the team—which also included coauthor Jean-Philippe Avouac, director of the TO—modeled an active region of the San Andreas Fault called the Parkfield segment. Located in central California, Parkfield produces magnitude-6 earthquakes every 20 years on average. They successfully created a series of earthquakes (ranging from magnitude 2 to 6) within the computer model, producing fault slip before, during, and after the earthquakes that closely matched the behavior observed in the past fifty years. 

"Our model explains some aspects of the seismic cycle at Parkfield that had eluded us, such as what causes changes in the amount of time between significant earthquakes and the jump in location where earthquakes nucleate, or begin," says Barbot.

The paper also demonstrates that a physical model of fault-slip evolution, based on laboratory experiments that measure how rock materials deform in the fault core, can explain many aspects of the earthquake cycle—and does so on a range of time scales. "Earthquake science is on the verge of building models that are based on the actual response of the rock materials as measured in the lab—models that can be tailored to reproduce a broad range of available observations for a given region," says Lapusta. "This implies we are getting closer to understanding the physical laws that govern how earthquakes nucleate, propagate, and arrest."

She says that they may be able to use models much like the one described in the Science paper to forecast the range of potential earthquakes on a fault segment, which could be used to further assess seismic hazard and improve building designs. 

Avouac agrees. "Currently, seismic hazard studies rely on what is known about past earthquakes," he says. "However, the relatively short recorded history may not be representative of all possibilities, especially rare extreme events. This gap can be filled with physical models that can be continuously improved as we learn more about earthquakes and laws that govern them."

"As computational resources and methods improve, dynamic simulations of even more realistic earthquake scenarios, with full account for dynamic interactions among faults, will be possible," adds Barbot. 

The Science study, "Under the Hood of the Earthquake Machine; Toward Predictive Modeling of the Seismic Cycle," was funded by grants from the Gordon and Betty Moore Foundation, the National Science Foundation, and the Southern California Earthquake Center.

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Katie Neith
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