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Behavior Matters: Redesigning the Clinical Trial












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Celebrating 11 Years of CARMA Discoveries



Dalmation Drawing

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Planet formation

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Molecular gas in galaxies

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Training the next generation



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Using Radar Satellites to Study Icelandic Volcanoes and Glaciers

On August 16 of last year, Mark Simons, a professor of geophysics at Caltech, landed in Reykjavik with 15 students and two other faculty members to begin leading a tour of the volcanic, tectonic, and glaciological highlights of Iceland. That same day, a swarm of earthquakes began shaking the island nation—seismicity that was related to one of Iceland's many volcanoes, Bárðarbunga caldera, which lies beneath Vatnajökull ice cap.

As the trip proceeded, it became clear to scientists studying the event that magma beneath the caldera was feeding a dyke, a vertical sheet of magma slicing through the crust in a northeasterly direction. On August 29, as the Caltech group departed Iceland, the dike triggered an eruption in a lava field called Holuhraun, about 40 kilometers (roughly 25 miles) from the caldera just beyond the northern limit of the ice cap.

Although the timing of the volcanic activity necessitated some shuffling of the trip's activities, such as canceling planned overnight visits near what was soon to become the eruption zone, it was also scientifically fortuitous. Simons is one of the leaders of a Caltech/JPL project known as the Advanced Rapid Imaging and Analysis (ARIA) program, which aims to use a growing constellation of international imaging radar satellites that will improve situational awareness, and thus response, following natural disasters. Under the ARIA umbrella, Caltech and JPL/NASA had already formed a collaboration with the Italian Space Agency (ASI) to use its COSMO-SkyMed (CSK) constellation (consisting of four orbiting X-Band radar satellites) following such events.

Through the ASI/ARIA collaboration, the managers of CSK agreed to target the activity at Bárðarbunga for imaging using a technique called interferometric synthetic aperture radar (InSAR). As two CSK satellites flew over, separated by just one day, they bounced signals off the ground to create images of the surface of the glacier above the caldera. By comparing those two images in what is called an interferogram, the scientists could see how the glacier surface had moved during that intervening day. By the evening of August 28, Simons was able to pull up that first interferogram on his cell phone. It showed that the ice above the caldera was subsiding at a rate of 50 centimeters (more than a foot and a half) a day—a clear indication that the magma chamber below Bárðarbunga caldera was deflating.

The next morning, before his return flight to the United States, Simons took the data to researchers at the University of Iceland who were tracking Bárðarbunga's activity.

"At that point, there had been no recognition that the caldera was collapsing. Naturally, they were focused on the dyke and all the earthquakes to the north," says Simons. "Our goal was just to let them know about the activity at the caldera because we were really worried about the possibility of triggering a subglacial melt event that would generate a catastrophic flood."

Luckily, that flood never happened, but the researchers at the University of Iceland did ramp up observations of the caldera with radar altimetry flights and installed a continuous GPS station on the ice overlying the center of the caldera.

Last December, Icelandic researchers published a paper in Nature about the Bárðarbunga event, largely focusing on the dyke and eruption. Now, completing the picture, Simons and his colleagues have developed a model to describe the collapsing caldera and the earthquakes produced by that action. The new findings appear in the journal Geophysical Journal International.

"Over a span of two months, there were more than 50 magnitude-5 earthquakes in this area. But they didn't look like regular faulting—like shearing a crack," says Simons. "Instead, the earthquakes looked like they resulted from movement inward along a vertical axis and horizontally outward in a radial direction—like an aluminum can when it's being crushed."

To try to determine what was actually generating the unusual earthquakes, Bryan Riel, a graduate student in Simons's group and lead author on the paper, used the original one-day interferogram of the Bárðarbunga area along with four others collected by CSK in September and October. Most of those one-day pairs spanned at least one of the earthquakes, but in a couple of cases, they did not. That allowed Riel to isolate the effect of the earthquakes and determine that most of the subsidence of the ice was due to what is called aseismic activity—the kind that does not produce big earthquakes. Thus, Riel was able to show that the earthquakes were not the primary cause of the surface deformation inferred from the satellite radar data.

"What we know for sure is that the magma chamber was deflating as the magma was feeding the dyke going northward," says Riel. "We have come up with two different models to explain what was actually generating the earthquakes."

In the first scenario, because the magma chamber deflated, pressure from the overlying rock and ice caused the caldera to collapse, producing the unusual earthquakes. This mechanism has been observed in cases of collapsing mines (e.g., the Crandall Canyon Mine in Utah).

The second model hypothesizes that there is a ring fault arcing around a significant portion of the caldera. As the magma chamber deflated, the large block of rock above it dropped but periodically got stuck on portions of the ring fault. As the block became unstuck, it caused rapid slip on the curved fault, producing the unusual earthquakes.

"Because we had access to these satellite images as well as GPS data, we have been able to produce two potential interpretations for the collapse of a caldera—a rare event that occurs maybe once every 50 to 100 years," says Simons. "To be able to see this documented as it's happening is truly phenomenal."

Additional authors on the paper, "The collapse of Bárðarbunga caldera, Iceland," are Hiroo Kanamori, John E. and Hazel S. Smits Professor of Geophysics, Emeritus, at Caltech; Pietro Milillo of the University of Basilicata in Potenza, Italy; Paul Lundgren of JPL; and Sergey Samsonov of the Canada Centre for Mapping and Earth Observation. The work was supported by a NASA Earth and Space Science Fellowship and by the Caltech/JPL President's and Director's Fund.

Kimm Fesenmaier
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Caltech Astronomers Observe a Supernova Colliding with Its Companion Star

Type Ia supernovae, one of the most dazzling phenomena in the universe, are produced when small dense stars called white dwarfs explode with ferocious intensity. At their peak, these supernovae can outshine an entire galaxy. Although thousands of supernovae of this kind were found in the last decades, the process by which a white dwarf becomes one has been unclear.

That began to change on May 3, 2014, when a team of Caltech astronomers working on a robotic observing system known as the intermediate Palomar Transient Factory (iPTF)—a multi-institute collaboration led by Shrinivas Kulkarni, the John D. and Catherine T. MacArthur Professor of Astronomy and Planetary Science and director of the Caltech Optical Observatories—discovered a Type Ia supernova, designated iPTF14atg, in nearby galaxy IC831, located 300 million light-years away.

The data that were immediately collected by the iPTF team lend support to one of two competing theories about the origin of white dwarf supernovae, and also suggest the possibility that there are actually two distinct populations of this type of supernova.

The details are outlined in a paper with Caltech graduate student Yi Cao the lead author, appearing May 21 in the journal Nature.

Type Ia supernovae are known as "standardizable candles" because they allow astronomers to gauge cosmic distances by how dim they appear relative to how bright they actually are. It is like knowing that, from one mile away, a light bulb looks 100 times dimmer than another located only one-tenth of a mile away. This consistency is what made these stellar objects instrumental in measuring the accelerating expansion of the universe in the 1990s, earning three scientists the Nobel Prize in Physics in 2011.

There are two competing origin theories, both starting with the same general scenario: the white dwarf that eventually explodes is one of a pair of stars orbiting around a common center of mass. The interaction between these two stars, the theories say, is responsible for triggering supernova development. What is the nature of that interaction? At this point, the theories diverge.

According to one theory, the so-called double-degenerate model, the companion to the exploding white dwarf is also a white dwarf, and the supernova explosion initiates when the two similar objects merge.

However, in the second theory, called the single-degenerate model, the second star is instead a sunlike star—or even a red giant, a much larger type of star. In this model, the white dwarf's powerful gravity pulls, or accretes, material from the second star. This process, in turn, increases the temperature and pressure in the center of the white dwarf until a runaway nuclear reaction begins, ending in a dramatic explosion.

The difficulty in determining which model is correct stems from the facts that supernova events are very rare—occurring about once every few centuries in our galaxy—and that the stars involved are very dim before the explosions.

That is where the iPTF comes in. From atop Palomar Mountain in Southern California, where it is mounted on the 48-inch Samuel Oschin Telescope, the project's fully automated camera optically surveys roughly 1000 square degrees of sky per night (approximately 1/20th of the visible sky above the horizon), looking for transients—objects, including Type Ia supernovae, whose brightness changes over timescales that range from hours to days.

On May 3, the iPTF took images of IC831 and transmitted the data for analysis to computers at the National Energy Research Scientific Computing Center, where a machine-learning algorithm analyzed the images and prioritized real celestial objects over digital artifacts. Because this first-pass analysis occurred when it was nighttime in the United States but daytime in Europe, the iPTF's European and Israeli collaborators were the first to sift through the prioritized objects, looking for intriguing signals. After they spotted the possible supernova—a signal that had not been visible in the images taken just the night before—the European and Israeli team alerted their U.S. counterparts, including Caltech graduate student and iPTF team member Yi Cao.

Cao and his colleagues then mobilized both ground- and space-based telescopes, including NASA's Swift satellite, which observes ultraviolet (UV) light, to take a closer look at the young supernova.

"My colleagues and I spent many sleepless nights on designing our system to search for luminous ultraviolet emission from baby Type Ia supernovae," says Cao. "As you can imagine, I was fired up when I first saw a bright spot at the location of this supernova in the ultraviolet image. I knew this was likely what we had been hoping for."

UV radiation has higher energy than visible light, so it is particularly suited to observing very hot objects like supernovae (although such observations are possible only from space, because Earth's atmosphere and ozone later absorbs almost all of this incoming UV). Swift measured a pulse of UV radiation that declined initially but then rose as the supernova brightened. Because such a pulse is short-lived, it can be missed by surveys that scan the sky less frequently than does the iPTF.

This observed ultraviolet pulse is consistent with a formation scenario in which the material ejected from a supernova explosion slams into a companion star, generating a shock wave that ignites the surrounding material. In other words, the data are in agreement with the single-degenerate model.

Back in 2010, Daniel Kasen, an associate professor of astronomy and physics at UC Berkeley and Lawrence Berkeley National Laboratory, used theoretical calculations and supercomputer simulations to predict just such a pulse from supernova-companion collisions. "After I made that prediction, a lot of people tried to look for that signature," Kasen says. "This is the first time that anyone has seen it. It opens up an entirely new way to study the origins of exploding stars."

According to Kulkarni, the discovery "provides direct evidence for the existence of a companion star in a Type Ia supernova, and demonstrates that at least some Type Ia supernovae originate from the single-degenerate channel."

Although the data from supernova iPTF14atg support it being made by a single-degenerate system, other Type Ia supernovae may result from double-degenerate systems. In fact, observations in 2011 of SN2011fe, another Type Ia supernova discovered in the nearby galaxy Messier 101 by PTF (the precursor to the iPTF), appeared to rule out the single-degenerate model for that particular supernova. And that means that both theories actually may be valid, says Caltech professor of theoretical astrophysics Sterl Phinney, who was not involved in the research. "The news is that it seems that both sets of theoretical models are right, and there are two very different kinds of Type Ia supernovae."

"Both rapid discovery of supernovae in their infancy by iPTF, and rapid follow-up by the Swift satellite, were essential to unveil the companion to this exploding white dwarf. Now we have to do this again and again to determine the fractions of Type Ia supernovae akin to different origin theories," says iPTF team member Mansi Kasliwal, who will join the Caltech astronomy faculty as an assistant professor in September 2015.

The iPTF project is a scientific collaboration between Caltech; Los Alamos National Laboratory; the University of Wisconsin–Milwaukee; the Oskar Klein Centre in Sweden; the Weizmann Institute of Science in Israel; the TANGO Program of the University System of Taiwan; and the Kavli Institute for the Physics and Mathematics of the Universe in Japan. The Caltech team is funded in part by the National Science Foundation.

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Dedication of Advanced LIGO

The Advanced LIGO Project, a major upgrade that will increase the sensitivity of the Laser Interferometer Gravitational-wave Observatories instruments by a factor of 10 and provide a 1,000-fold increase in the number of astrophysical candidates for gravitational wave signals, was officially dedicated today in a ceremony held at the LIGO Hanford facility in Richland, Washington.


The dedication ceremony featured remarks from Caltech president Thomas F. Rosenbaum, the Sonja and William Davidow Presidential Chair and professor of physics; Professor of Physics Tom Soifer (BS '68), the Kent and Joyce Kresa Leadership Chair of Caltech's Division of Physics, Mathematics and Astronomy; and NSF director France Córdova (PhD '79).


"Advanced LIGO represents a critically important step forward in our continuing effort to understand the extraordinary mysteries of our universe," says Córdova. "It gives scientists a highly sophisticated instrument for detecting gravitational waves, which we believe carry with them information about their dynamic origins and about the nature of gravity that cannot be obtained by conventional astronomical tools."

"This is a particularly thrilling event, marking the opening of a new window on the universe, one that will allow us to see the final cataclysmic moments in the lives of stars that would otherwise be invisible to us," says Soifer.




The original configuration of LIGO was sensitive enough to detect a change in the lengths of the 4-km arms by a distance one-thousandth the size of a proton; this is like accurately measuring the distance from Earth to the nearest star—3 light years—to within the width of a human hair. Advanced LIGO, which will utilize the infrastructure of LIGO, will be 10 times more sensitive.




LIGO research is carried out by the LIGO Scientific Collaboration (LSC), a group of some 950 scientists at universities around the United States and in 15 other countries. The LSC network includes the LIGO interferometers and the GEO600 interferometer, located near Hannover, Germany, and theand and the LSC works jointly with the Virgo Collaboration—which designed and constructed the 3-km-long Virgo interferometer located in Cascina, Italy—to analyze data from the LIGO, GEO, and Virgo interferometers.

Several international partners including the Max Planck Institute for Gravitational Physics, the Albert Einstein Institute, the Laser Zentrum Hannover, and the Leibniz Universität Hannover in Germany; an Australian consortium of universities, led by the Australian National University and the University of Adelaide, and supported by the Australian Research Council; partners in the United Kingdom funded by the Science and Technology Facilities Council; and the University of Florida and Columbia University, provided significant contributions of equipment, labor, and expertise.

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Controlling a Robotic Arm with a Patient's Intentions








Andersen and his colleagues wanted to improve the versatility of movement that a neuroprosthetic can offer by recording signals from a different brain region—the PPC. "The PPC is earlier in the pathway, so signals there are more related to movement planning—what you actually intend to do—rather than the details of the movement execution," he says. "We hoped that the signals from the PPC would be easier for the patients to use, ultimately making the movement process more intuitive. Our future studies will investigate ways to combine the detailed motor cortex signals with more cognitive PPC signals to take advantage of each area's specializations."

In the clinical trial, designed to test the safety and effectiveness of this new approach, the Caltech team collaborated with surgeons at Keck Medicine of USC and the rehabilitation team at Rancho Los Amigos National Rehabilitation Center. The surgeons implanted a pair of small electrode arrays in two parts of the PPC of a quadriplegic patient. Each array contains 96 active electrodes that, in turn, each record the activity of a single neuron in the PPC. The arrays were connected by a cable to a system of computers that processed the signals, decoded the intent of the subject, and controlled output devices that included a computer cursor and a robotic arm developed by collaborators at Johns Hopkins University.



"It was a big surprise that the patient was able to control the limb on day one—the very first day he tried," he adds. "This attests to how intuitive the control is when using PPC activity."

The patient, Erik G. Sorto, was also thrilled with the quick results: "I was surprised at how easy it was," he says. "I remember just having this out-of-body experience, and I wanted to just run around and high-five everybody."

Over time, Sorto continued to refine his control of his robotic arm, thus providing the researchers with more information about how the PPC works. For example, "we learned that if he thought, 'I should move my hand over toward to the object in a certain way'—trying to control the limb—that didn't work," Andersen says. "The thought actually needed to be more cognitive. But if he just thought, 'I want to grasp the object,' it was much easier. And that is exactly what we would expect from this area of the brain."

This better understanding of the PPC will help the researchers improve neuroprosthetic devices of the future, Andersen says. "What we have here is a unique window into the workings of a complex high-level brain area as we work collaboratively with our subject to perfect his skill in controlling external devices."

"The primary mission of the USC Neurorestoration Center is to take advantage of resources from our clinical programs to create unique opportunities to translate scientific discoveries, such as those of the Andersen Lab at Caltech, to human patients, ultimately turning transformative discoveries into effective therapies," says center director Charles Y. Liu, professor of neurological surgery, neurology, and biomedical engineering at USC, who led the surgical implant procedure and the USC/Rancho Los Amigos team in the collaboration.


Dr. Mindy Aisen, the chief medical officer at Rancho Los Amigos who led the study's rehabilitation team, says that advancements in prosthetics like these hold promise for the future of patient rehabilitation. "We at Rancho are dedicated to advancing rehabilitation through new assistive technologies, such as robotics and brain-machine interfaces. We have created a unique environment that can seamlessly bring together rehabilitation, medicine, and science as exemplified in this study," she says.

Although tasks like shaking hands and playing "rock, paper, scissors" are important to demonstrate the capability of these devices, the hope is that neuroprosthetics will eventually enable patients to perform more practical tasks that will allow them to regain some of their independence.



Although Sorto's implant allowed him to control larger movements with visual feedback, "to really do fine dexterous control, you also need feedback from touch," Andersen says. "Without it, it's like going to the dentist and having your mouth numbed. It's very hard to speak without somatosensory feedback." The newest devices under development by Andersen and his colleagues feature a mechanism to relay signals from the robotic arm back into the part of the brain that gives the perception of touch.

"The reason we are developing these devices is that normally a quadriplegic patient couldn't, say, pick up a glass of water to sip it, or feed themselves. They can't even do anything if their nose itches. Seemingly trivial things like this are very frustrating for the patients," Andersen says. "This trial is an important step toward improving their quality of life."

The results of the trial were published in a paper titled, "Decoding Motor Imagery from the Posterior Parietal Cortex of a Tetraplegic Human." The implanted device and signal processors used in the Caltech-led clinical trial were the NeuroPort Array and NeuroPort Bio-potential Signal Processors developed by Blackrock Microsystems in Salt Lake City, Utah. The robotic arm used in the trial was the Modular Prosthetic Limb, developed at the Applied Physics Laboratory at Johns Hopkins. Sorto was recruited to the trial by collaborators at Rancho Los Amigos National Rehabilitation Center and at Keck Medicine of USC. This trial was funded by National Institutes of Health, the Boswell Foundation, the Department of Defense, and the USC Neurorestoration Center.

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Do Fruit Flies Have Emotions?

A fruit fly starts buzzing around food at a picnic, so you wave your hand over the insect and shoo it away. But when the insect flees the scene, is it doing so because it is actually afraid? Using fruit flies to study the basic components of emotion, a new Caltech study reports that a fly's response to a shadowy overhead stimulus might be analogous to a negative emotional state such as fear—a finding that could one day help us understand the neural circuitry involved in human emotion.

The study, which was done in the laboratory of David Anderson, Seymour Benzer Professor of Biology and an investigator with the Howard Hughes Medical Institute, was published online May 14 in the journal Current Biology.

Insects are an important model for the study of emotion; although mice are closer to humans on the evolutionary family tree, the fruit fly has a much simpler neurological system that is easier to study. However, studying emotions in insects or any other animal can also be tricky. Because researchers know the experience of human emotion, they might anthropomorphize those of an insect—just as you might assume that the shooed-away fly left your plate because it was afraid of your hand. But there are several problems with such an assumption, says postdoctoral scholar William T. Gibson, first author of the paper.

"There are two difficulties with taking your own experiences and then saying that maybe these are happening in a fly. First, a fly's brain is very different from yours, and second, a fly's evolutionary history is so different from yours that even if you could prove beyond any doubt that flies have emotions, those emotions probably wouldn't be the same ones that you have," he says. "For these reasons, in our study, we wanted to take an objective approach."

Anderson and Gibson and their colleagues did this by deconstructing the idea of an emotion into basic building blocks—so-called emotion primitives, a concept previously developed by Anderson and Ralph Adolphs, Bren Professor of Psychology and Neuroscience and professor of biology.

"There has been ongoing debate for decades about what 'emotion' means, and there is no generally accepted definition. In an article that Ralph Adolphs and I recently wrote, we put forth the view that emotions are a type of internal brain state with certain general properties that can exist independently of subjective, conscious feelings, which can only be studied in humans," Anderson says. "That means we can study such brain states in animal models like flies or mice without worrying about whether they have 'feelings' or not. We use the behaviors that express those states as a readout."

Gibson explains by analogy that emotions can be broken down into these emotion primitives much as a secondary color, such as orange, can be separated into two primary colors, yellow and red. "And if we can show that fruit flies display all of these separate but necessary primitives, we then may be able to make the argument that they also have an emotion, like fear."

The emotion primitives analyzed in the fly study can be understood in the context of a stimulus associated with human fear: the sound of a gunshot. If you hear a gun fire, the sound may trigger a negative feeling. This feeling, a primitive called valence, will probably cause you to behave differently for several minutes afterward. This is a primitive called persistence. Repeated exposure to the stimulus should also produce a greater emotional response—a primitive called scalability; for example, the sound of 10 gunshots would make you more afraid than the sound of one shot.

Gibson says that another primitive of fear is that it is generalized to different contexts, meaning that if you were eating lunch or were otherwise occupied when the gun fired, the fear would take over, distracting you from your lunch. Trans-situationality is another primitive that could cause you to produce the same fearful reaction in response to an unrelated stimulus—such as the sound of a car backfiring.

The researchers chose to study these five primitives by observing the insects in the presence of a fear-inducing stimulus. Because defensive behavioral responses to overhead visual threats are common in many animals, the researchers created an apparatus that would pass a dark paddle over the flies' habitat. The flies' movements were then tracked using a software program created in collaboration with Pietro Perona, the Allen E. Puckett Professor of Electrical Engineering.

The researchers analyzed the flies' responses to the stimulus and found that the insects displayed all of these emotion primitives. For example, responses were scalable: when the paddle passed overhead, the flies would either freeze, or jump away from the stimulus, or enter a state of elevated arousal, and each response increased with the number of times the stimulus was delivered. And when hungry flies were gathered around food, the stimulus would cause them to leave the food for several seconds and run around the arena until their state of elevated arousal decayed and they returned to the food—exhibiting the primitives of context generalization and persistence.

"These experiments provide objective evidence that visual stimuli designed to mimic an overhead predator can induce a persistent and scalable internal state of defensive arousal in flies, which can influence their subsequent behavior for minutes after the threat has passed," Anderson says. "For us, that's a big step beyond just casually intuiting that a fly fleeing a visual threat must be 'afraid,' based on our anthropomorphic assumptions. It suggests that the flies' response to the threat is richer and more complicated than a robotic-like avoidance reflex."

In the future, the researchers say that they plan to combine the new technique with genetically based techniques and imaging of brain activity to identify the neural circuitry that underlies these defensive behaviors. Their end goal is to identify specific populations of neurons in the fruit fly brain that are necessary for emotion primitives—and whether these functions are conserved in higher organisms, such as mice or even humans.

Although the presence of these primitives suggests that the flies might be reacting to the stimulus based on some kind of emotion, the researchers are quick to point out that this new information does not prove—nor did it set out to establish—that flies can experience fear, or happiness, or anger, or any other feelings.

"Our work can get at questions about mechanism and questions about the functional properties of emotion states, but we cannot get at the question of whether or not flies have feelings," Gibson says.

The study, titled "Behavioral Responses to a Repetitive Stimulus Express a Persistent State of Defensive Arousal in Drosophila," was published in the journal Current Biology. In addition to Gibson, Anderson, and Perona, Caltech coauthors include graduate student Carlos Gonzalez, undergraduate Rebecca Du, former research assistants Conchi Fernandez and Panna Felsen (BS '09, MS '10), and former postdoctoral scholar Michael Maire. Coauthors Lakshminarayanan Ramasamy and Tanya Tabachnik are from the Janelia Research Campus of the Howard Hughes Medical Institute (HHMI). The work was funded by the National Institutes of Health, HHMI, and the Gordon and Betty Moore Foundation.

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