A Stepping-Stone for Oxygen on Earth

Caltech researchers find evidence of an early manganese-oxidizing photosystem

For most terrestrial life on Earth, oxygen is necessary for survival. But the planet's atmosphere did not always contain this life-sustaining substance, and one of science's greatest mysteries is how and when oxygenic photosynthesis—the process responsible for producing oxygen on Earth through the splitting of water molecules—first began. Now, a team led by geobiologists at the California Institute of Technology (Caltech) has found evidence of a precursor photosystem involving manganese that predates cyanobacteria, the first group of organisms to release oxygen into the environment via photosynthesis.  

The findings, outlined in the June 24 early edition of the Proceedings of the National Academy of Sciences (PNAS), strongly support the idea that manganese oxidation—which, despite the name, is a chemical reaction that does not have to involve oxygen—provided an evolutionary stepping-stone for the development of water-oxidizing photosynthesis in cyanobacteria.

"Water-oxidizing or water-splitting photosynthesis was invented by cyanobacteria approximately 2.4 billion years ago and then borrowed by other groups of organisms thereafter," explains Woodward Fischer, assistant professor of geobiology at Caltech and a coauthor of the study. "Algae borrowed this photosynthetic system from cyanobacteria, and plants are just a group of algae that took photosynthesis on land, so we think with this finding we're looking at the inception of the molecular machinery that would give rise to oxygen."

Photosynthesis is the process by which energy from the sun is used by plants and other organisms to split water and carbon dioxide molecules to make carbohydrates and oxygen. Manganese is required for water splitting to work, so when scientists began to wonder what evolutionary steps may have led up to an oxygenated atmosphere on Earth, they started to look for evidence of manganese-oxidizing photosynthesis prior to cyanobacteria. Since oxidation simply involves the transfer of electrons to increase the charge on an atom—and this can be accomplished using light or O2—it could have occurred before the rise of oxygen on this planet.

"Manganese plays an essential role in modern biological water splitting as a necessary catalyst in the process, so manganese-oxidizing photosynthesis makes sense as a potential transitional photosystem," says Jena Johnson, a graduate student in Fischer's laboratory at Caltech and lead author of the study.

To test the hypothesis that manganese-based photosynthesis occurred prior to the evolution of oxygenic cyanobacteria, the researchers examined drill cores (newly obtained by the Agouron Institute) from 2.415 billion-year-old South African marine sedimentary rocks with large deposits of manganese.

Manganese is soluble in seawater. Indeed, if there are no strong oxidants around to accept electrons from the manganese, it will remain aqueous, Fischer explains, but the second it is oxidized, or loses electrons, manganese precipitates, forming a solid that can become concentrated within seafloor sediments.

"Just the observation of these large enrichments—16 percent manganese in some samples—provided a strong implication that the manganese had been oxidized, but this required confirmation," he says.

To prove that the manganese was originally part of the South African rock and not deposited there later by hydrothermal fluids or some other phenomena, Johnson and colleagues developed and employed techniques that allowed the team to assess the abundance and oxidation state of manganese-bearing minerals at a very tiny scale of 2 microns.

"And it's warranted—these rocks are complicated at a micron scale!" Fischer says. "And yet, the rocks occupy hundreds of meters of stratigraphy across hundreds of square kilometers of ocean basin, so you need to be able to work between many scales—very detailed ones, but also across the whole deposit to understand the ancient environmental processes at work."

Using these multiscale approaches, Johnson and colleagues demonstrated that the manganese was original to the rocks and first deposited in sediments as manganese oxides, and that manganese oxidation occurred over a broad swath of the ancient marine basin during the entire timescale captured by the drill cores.

"It's really amazing to be able to use X-ray techniques to look back into the rock record and use the chemical observations on the microscale to shed light on some of the fundamental processes and mechanisms that occurred billions of years ago," says Samuel Webb, coauthor on the paper and beam line scientist at the SLAC National Accelerator Laboratory at Stanford University, where many of the study's experiments took place. "Questions regarding the evolution of the photosynthetic pathway and the subsequent rise of oxygen in the atmosphere are critical for understanding not only the history of our own planet, but also the basics of how biology has perfected the process of photosynthesis."

Once the team confirmed that the manganese had been deposited as an oxide phase when the rock was first forming, they checked to see if these manganese oxides were actually formed before water-splitting photosynthesis or if they formed after as a result of reactions with oxygen. They used two different techniques to check whether oxygen was present. It was not—proving that water-splitting photosynthesis had not yet evolved at that point in time. The manganese in the deposits had indeed been oxidized and deposited before the appearance of water-splitting cyanobacteria. This implies, the researchers say, that manganese-oxidizing photosynthesis was a stepping-stone for oxygen-producing, water-splitting photosynthesis.

"I think that there will be a number of additional experiments that people will now attempt to try and reverse engineer a manganese photosynthetic photosystem or cell," Fischer says. "Once you know that this happened, it all of a sudden gives you reason to take more seriously an experimental program aimed at asking, 'Can we make a photosystem that's able to oxidize manganese but doesn't then go on to split water? How does it behave, and what is its chemistry?' Even though we know what modern water splitting is and what it looks like, we still don't know exactly how it works. There is still a major discovery to be made to find out exactly how the catalysis works, and now knowing where this machinery comes from may open new perspectives into its function—an understanding that could help target technologies for energy production from artificial photosynthesis. "

Next up in Fischer's lab, Johnson plans to work with others to try and mutate a cyanobacteria to "go backwards" and perform manganese-oxidizing photosynthesis. The team also plans to investigate a set of rocks from western Australia that are similar in age to the samples used in the current study and may also contain beds of manganese. If their current study results are truly an indication of manganese-oxidizing photosynthesis, they say, there should be evidence of the same processes in other parts of the world.

"Oxygen is the backdrop on which this story is playing out on, but really, this is a tale of the evolution of this very intense metabolism that happened once—an evolutionary singularity that transformed the planet," Fischer says. "We've provided insight into how the evolution of one of these remarkable molecular machines led up to the oxidation of our planet's atmosphere, and now we're going to follow up on all angles of our findings."

Funding for the research outlined in the PNAS paper, titled "Manganese-oxidizing photosynthesis before the rise of cyanobacteria," was provided by the Agouron Institute, NASA's Exobiology Branch, the David and Lucile Packard Foundation, and the National Science Foundation Graduate Research Fellowship program. Joseph Kirschvink, Nico and Marilyn Van Wingen Professor of Geobiology at Caltech, also contributed to the study along with Katherine Thomas and Shuhei Ono from the Massachusetts Institute of Technology.

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Beauty and the Brain: Electrical Stimulation of the Brain Makes You Perceive Faces as More Attractive

Findings may lead to promising ways to treat and study neuropsychiatric disorders

Beauty is in the eye of the beholder, and—as researchers have now shown—in the brain as well.

The researchers, led by scientists at the California Institute of Technology (Caltech), have used a well-known, noninvasive technique to electrically stimulate a specific region deep inside the brain previously thought to be inaccessible. The stimulation, the scientists say, caused volunteers to judge faces as more attractive than before their brains were stimulated.

Being able to effect such behavioral changes means that this electrical stimulation tool could be used to noninvasively manipulate deep regions of the brain—and, therefore, that it could serve as a new approach to study and treat a variety of deep-brain neuropsychiatric disorders, such as Parkinson's disease and schizophrenia, the researchers say.

"This is very exciting because the primary means of inducing these kinds of deep-brain changes to date has been by administering drug treatments," says Vikram Chib, a postdoctoral scholar who led the study, which is being published in the June 11 issue of the journal Translational Psychiatry. "But the problem with drugs is that they're not location-specific—they act on the entire brain." Thus, drugs may carry unwanted side effects or, occasionally, won't work for certain patients—who then may need invasive treatments involving the implantation of electrodes into the brain.

So Chib and his colleagues turned to a technique called transcranial direct-current stimulation (tDCS), which, Chib notes, is cheap, simple, and safe. In this method, an anode and a cathode are placed at two different locations on the scalp. A weak electrical current—which can be powered by a nine-volt battery—runs from the cathode, through the brain, and to the anode. The electrical current is a mere 2 milliamps—10,000 times less than the 20 amps typically available from wall sockets. "All you feel is a little bit of tingling, and some people don't even feel that," he says.

"There have been many studies employing tDCS to affect behavior or change local neural activity," says Shinsuke Shimojo, the Gertrude Baltimore Professor of Experimental Psychology and a coauthor of the paper. For example, the technique has been used to treat depression and to help stroke patients rehabilitate their motor skills. "However, to our knowledge, virtually none of the previous studies actually examined and correlated both behavior and neural activity," he says. These studies also targeted the surface areas of the brain—not much more than a centimeter deep—which were thought to be the physical limit of how far tDCS could reach, Chib adds.

The researchers hypothesized that they could exploit known neural connections and use tDCS to stimulate deeper regions of the brain. In particular, they wanted to access the ventral midbrain—the center of the brain's reward-processing network, and about as deep as you can go. It is thought to be the source of dopamine, a chemical whose deficiency has been linked to many neuropsychiatric disorders.

The ventral midbrain is part of a neural circuit that includes the dorsolateral prefrontal cortex (DLPFC), which is located just above the temples, and the ventromedial prefrontal cortex (VMPFC), which is behind the forehead. Decreasing activity in the DLPFC boosts activity in the VMPFC, which in turn bumps up activity in the ventral midbrain. To manipulate the ventral midbrain, therefore, the researchers decided to try using tDCS to deactivate the DLPFC and activate the VMPFC.

To test their hypothesis, the researchers asked volunteers to judge the attractiveness of groups of faces both before and after the volunteers' brains had been stimulated with tDCS. Judging facial attractiveness is one of the simplest, most primal tasks that can activate the brain's reward network, and difficulty in evaluating faces and recognizing facial emotions is a common symptom of neuropsychiatric disorders. The study participants rated the faces while inside a functional magnetic resonance imaging (fMRI) scanner, which allowed the researchers to evaluate any changes in brain activity caused by the stimulation.

A total of 99 volunteers participated in the tDCS experiment and were divided into six stimulation groups. In the main stimulation group, composed of 19 subjects, the DLPFC was deactivated and the VMPFC activated with a stimulation configuration that the researchers theorized would ultimately activate the ventral midbrain. The other groups were used to test different stimulation configurations. For example, in one group, the placement of the cathode and anode were switched so that the DLPFC was activated and the VMPFC was deactivated—the opposite of the main group. Another was a "sham" group, in which the electrodes were placed on volunteers' heads, but no current was run.

Those in the main group rated the faces presented after stimulation as more attractive than those they saw before stimulation. There were no differences in the ratings from the control groups. This change in ratings in the main group suggests that tDCS is indeed able to activate the ventral midbrain, and that the resulting changes in brain activity in this deep-brain region are associated with changes in the evaluation of attractiveness.

In addition, the fMRI scans revealed that tDCS strengthened the correlation between VMPFC activity and ventral midbrain activity. In other words, stimulation appeared to enhance the neural connectivity between the two brain areas. And for those who showed the strongest connectivity, tDCS led to the biggest change in attractiveness ratings. Taken together, the researchers say these results show that tDCS is causing those shifts in perception by manipulating the ventral midbrain via the DLPFC and VMPFC.

"The fact that we haven't had a way to noninvasively manipulate a functional circuit in the brain has been a fundamental bottleneck in human behavioral neuroscience," Shimojo says. This new work, he adds, represents a big first step in removing that bottleneck.

Using tDCS to study and treat neuropsychiatric disorders hinges on the assumption that the technique directly influences dopamine production in the ventral midbrain, Chib explains. But because fMRI can't directly measure dopamine, this study was unable to make that determination. The next step, then, is to use methods that can—such as positron emission tomography (PET) scans.

More work also needs to be done to see how tDCS may be used for treating disorders and to precisely determine the duration of the stimulation effects—as a rule of thumb, the influence of tDCS lasts for twice the exposure time, Chib says. Future studies will also be needed to see what other behaviors this tDCS method can influence. Ultimately, clinical tests will be needed for medical applications.

In addition to Chib and Shimojo, the other authors of the paper are Kyongsik Yun, a former postdoctoral scholar at Caltech who is now at the Korea Advanced Institute of Science and Technology (KAIST), and Hidehiko Takahashi of the Kyoto University Graduate School of Medicine. The title of the Translational Psychiatry paper is "Noninvasive remote activation of the ventral midbrain by transcranial direct current stimulation of prefrontal cortex." This work was funded by the Exploratory Research for Advanced Technology (ERATO) and CREST programs of the Japan Science and Technology Agency (JST); the Caltech-Tamagawa gCOE (Global Center of Excellence) program; and a Japan-U.S. Brain Research Cooperative Program grant.

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Keeping Stem Cells Strong

Caltech biologists show that an RNA molecule protects stem cells during inflammation

When infections occur in the body, stem cells in the blood often jump into action by multiplying and differentiating into mature immune cells that can fight off illness. But repeated infections and inflammation can deplete these cell populations, potentially leading to the development of serious blood conditions such as cancer. Now, a team of researchers led by biologists at the California Institute of Technology (Caltech) has found that, in mouse models, the molecule microRNA-146a (miR-146a) acts as a critical regulator and protector of blood-forming stem cells (called hematopoietic stem cells, or HSCs) during chronic inflammation, suggesting that a deficiency of miR-146a may be one important cause of blood cancers and bone marrow failure.

The team came to this conclusion by developing a mouse model that lacks miR-146a. RNA is a polymer structured like DNA, the chemical that makes up our genes. MicroRNAs, as the name implies, are a class of very short RNAs that can interfere with or regulate the activities of particular genes. When subjected to a state of chronic inflammation, mice lacking miR-146a showed a decline in the overall number and quality of their HSCs; normal mice producing the molecule, in contrast, were better able to maintain their levels of HSCs despite long-term inflammation. The researchers' findings are outlined in the May 21 issue of the new journal eLIFE.

"This mouse with genetic deletion of miR-146a is a wonderful model with which to understand chronic-inflammation-driven tumor formation and hematopoietic stem cell biology during chronic inflammation," says Jimmy Zhao, the lead author of the study and an MD/PhD student in the Caltech laboratory of David Baltimore, the Robert Andrews Millikan Professor of Biology. "It was surprising that a single microRNA plays such a crucial role. Deleting it produced a profound and dramatic pathology, which clearly highlights the critical and indispensable function of miR-146a in guarding the quality and longevity of HSCs."

The study findings provide, for the first time, a detailed molecular connection between chronic inflammation, and bone marrow failure and diseases of the blood. These findings could lead to the discovery and development of anti-inflammatory molecules that could be used as therapeutics for blood diseases. In fact, the researchers believe that miR-146a itself may ultimately become a very effective anti-inflammatory molecule, once RNA molecules or mimetics can be delivered more efficiently to the cells of interest.

The new mouse model, Zhao says, also mimics important aspects of human myelodysplastic syndrome (MDS)—a form of pre-leukemia that often causes severe anemia, can require frequent blood transfusions, and usually leads to acute myeloid leukemia. Further study of the model could lead to a better understanding of the condition and therefore potential new treatments for MDS.

"This study speaks to the importance of keeping chronic inflammation in check and provides a good rationale for broad use of safer and more effective anti-inflammatory molecules," says Baltimore, who is a coauthor of the study. "If we can understand what cell types and proteins are critically important in chronic-inflammation-driven tumor formation and stem cell exhaustion, we can potentially design better and safer drugs to intervene."

Funding for the research outlined in the eLIFE paper, titled "MicroRNA-146a acts as a guardian of the quality and longevity of hematopoietic stem cells in mice," was provided by the National Institute of Allergy and Infectious Disease; the National Heart, Lung, and Blood Institute; and the National Cancer Institute. Yvette Garcia-Flores, the lead technician in Baltimore's lab, also contributed to the study along with Dinesh Rao from UCLA and Ryan O'Connell from the University of Utah. eLIFE, a new open-access, high-impact journal, is backed by three of the world's leading funding agencies, the Howard Hughes Medical Institute, the Max Planck Society, and the Wellcome Trust. 

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Birth of a Black Hole

A new kind of cosmic flash may reveal something never seen before: the birth of a black hole.

When a massive star exhausts its fuel, it collapses under its own gravity and produces a black hole, an object so dense that not even light can escape its gravitational grip. According to a new analysis by an astrophysicist at the California Institute of Technology (Caltech), just before the black hole forms, the dying star may generate a distinct burst of light that will allow astronomers to witness the birth of a new black hole for the first time.

Tony Piro, a postdoctoral scholar at Caltech, describes this signature light burst in a paper published in the May 1 issue of the Astrophysical Journal Letters. While some dying stars that result in black holes explode as gamma-ray bursts, which are among the most energetic phenomena in the universe, those cases are rare, requiring exotic circumstances, Piro explains. "We don't think most run-of-the-mill black holes are created that way." In most cases, according to one hypothesis, a dying star produces a black hole without a bang or a flash: the star would seemingly vanish from the sky—an event dubbed an unnova. "You don't see a burst," he says. "You see a disappearance."

But, Piro hypothesizes, that may not be the case. "Maybe they're not as boring as we thought," he says.

According to well-established theory, when a massive star dies, its core collapses under its own weight. As it collapses, the protons and electrons that make up the core merge and produce neutrons. For a few seconds—before it ultimately collapses into a black hole—the core becomes an extremely dense object called a neutron star, which is as dense as the sun would be if squeezed into a sphere with a radius of about 10 kilometers (roughly 6 miles). This collapsing process also creates neutrinos, which are particles that zip through almost all matter at nearly the speed of light. As the neutrinos stream out from the core, they carry away a lot of energy—representing about a tenth of the sun's mass (since energy and mass are equivalent, per E = mc2).

According to a little-known paper written in 1980 by Dmitry Nadezhin of the Alikhanov Institute for Theoretical and Experimental Physics in Russia, this rapid loss of mass means that the gravitational strength of the dying star's core would abruptly drop. When that happens, the outer gaseous layers—mainly hydrogen—still surrounding the core would rush outward, generating a shock wave that would hurtle through the outer layers at about 1,000 kilometers per second (more than 2 million miles per hour).

Using computer simulations, two astronomers at UC Santa Cruz, Elizabeth Lovegrove and Stan Woosley, recently found that when the shock wave strikes the outer surface of the gaseous layers, it would heat the gas at the surface, producing a glow that would shine for about a year—a potentially promising signal of a black-hole birth. Although about a million times brighter than the sun, this glow would be relatively dim compared to other stars. "It would be hard to see, even in galaxies that are relatively close to us," says Piro.

But now Piro says he has found a more promising signal. In his new study, he examines in more detail what might happen at the moment when the shock wave hits the star's surface, and he calculates that the impact itself would make a flash 10 to 100 times brighter than the glow predicted by Lovegrove and Woosley. "That flash is going to be very bright, and it gives us the best chance for actually observing that this event occurred," Piro explains. "This is what you really want to look for."

Such a flash would be dim compared to exploding stars called supernovae, for example, but it would be luminous enough to be detectable in nearby galaxies, he says. The flash, which would shine for 3 to 10 days before fading, would be very bright in optical wavelengths—and at its very brightest in ultraviolet wavelengths.

Piro estimates that astronomers should be able to see one of these events per year on average. Surveys that watch the skies for flashes of light like supernovae—surveys such as the Palomar Transient Factory (PTF), led by Caltech—are well suited to discover these unique events, he says. The intermediate Palomar Transient Factory (iPTF), which improves on the PTF and just began surveying in February, may be able to find a couple of these events per year.

Neither survey has observed any black-hole flashes as of yet, says Piro, but that does not rule out their existence. "Eventually we're going to start getting worried if we don't find these things." But for now, he says, his expectations are perfectly sound.

With Piro's analysis in hand, astronomers should be able to design and fine-tune additional surveys to maximize their chances of witnessing a black-hole birth in the near future. In 2015, the next generation of PTF, called the Zwicky Transient Facility (ZTF), is slated to begin; it will be even more sensitive, improving by several times the chances of finding those flashes. "Caltech is therefore really well-positioned to look for transient events like this," Piro says.

Within the next decade, the Large Synoptic Survey Telescope (LSST) will begin a massive survey of the entire night sky. "If LSST isn't regularly seeing these kinds of events, then that's going to tell us that maybe there's something wrong with this picture, or that black-hole formation is much rarer than we thought," he says.

The Astrophysical Journal Letters paper is titled "Taking the 'un' out of unnovae." This research was supported by the National Science Foundation, NASA, and the Sherman Fairchild Foundation.

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Astronomers Discover Massive Star Factory in Early Universe

Star-forming galaxy is the most distant ever found

PASADENA, Calif.—Smaller begets bigger.

Such is often the case for galaxies, at least: the first galaxies were small, then eventually merged together to form the behemoths we see in the present universe.

Those smaller galaxies produced stars at a modest rate; only later—when the universe was a couple of billion years old—did the vast majority of larger galaxies begin to form and accumulate enough gas and dust to become prolific star factories. Indeed, astronomers have observed that these star factories—called starburst galaxies—became prevalent a couple of billion years after the Big Bang.

But now a team of astronomers, which includes several from the California Institute of Technology (Caltech), has discovered a dust-filled, massive galaxy churning out stars when the cosmos was a mere 880 million years old—making it the earliest starburst galaxy ever observed.

The galaxy is about as massive as our Milky Way, but produces stars at a rate 2,000 times greater, which is a rate as high as any galaxy in the universe. Generating the mass equivalent of 2,900 suns per year, the galaxy is especially prodigious—prompting the team to call it a "maximum-starburst" galaxy.

"Massive, intense starburst galaxies are expected to only appear at later cosmic times," says Dominik Riechers, who led the research while a senior research fellow at Caltech. "Yet, we have discovered this colossal starburst just 880 million years after the Big Bang, when the universe was at little more than 6 percent of its current age." Now an assistant professor at Cornell, Riechers is the first author of the paper describing the findings in the April 18 issue of the journal Nature.

While the discovery of this single galaxy isn't enough to overturn current theories of galaxy formation, finding more galaxies like this one could challenge those theories, the astronomers say. At the very least, theories will have to be modified to explain how this galaxy, dubbed HFLS3, formed, Riechers says.

"This galaxy is just one spectacular example, but it's telling us that extremely vigorous star formation was possible early in the universe," says Jamie Bock, professor of physics at Caltech and a coauthor of the paper.

The astronomers found HFLS3 chock full of molecules such as carbon monoxide, ammonia, hydroxide, and even water. Because most of the elements in the universe—other than hydrogen and helium—are fused in the nuclear furnaces of stars, such a rich and diverse chemical composition is indicative of active star formation. And indeed, Bock says, the chemical composition of HFLS3 is similar to those of other known starburst galaxies that existed later in cosmic history.

Last month, a Caltech-led team of astronomers—a few of whom are also authors on this newer work—discovered dozens of similar galaxies that were producing stars as early as 1.5 billion years after the Big Bang. But none of them existed as early as HFLS3, which has been studied in much greater detail.

Those previous observations were made possible by gravitational lensing, in which large foreground galaxies act as cosmic magnifying glasses, bending the light of the starburst galaxies and making their detection easier. HFLS3, however, is only weakly lensed, if at all. The fact that it was detectable without the help of lensing means that it is intrinsically a bright galaxy in far-infrared light—nearly 30 trillion times as luminous as the sun and 2,000 times more luminous than the Milky Way.

Because the galaxy is enshrouded in dust, it's very faint in visible light. The galaxy's stars, however, heat up the dust, causing it to radiate in infrared wavelengths. The astronomers were able to find HFLS3 as they sifted through data taken by the European Space Agency's Herschel Space Observatory, which studies the infrared universe. The data was part of the Herschel Multi-tiered Extragalactic Survey (HerMES), an effort co-coordinated by Bock to observe a large patch of the sky (roughly 1,300 times the size of the moon) with Herschel.

Amid the thousands of galaxies detected in the survey, HFLS3 appeared as just a faint dot—but a particularly red one. That caught the attention of Darren Dowell, a visiting associate at Caltech who was analyzing the HerMES data. The object's redness meant that its light was being substantially stretched toward longer (and redder) wavelengths by the expansion of the universe. The more distant an object, the more its light is stretched, and so a very red source would be very far away. The only other possibility would be that—because cooler objects emit light at longer wavelengths—the object might be unusually cold; the astronomers' analysis, however, ruled out that possibility. Because it takes the light billions of years to travel across space, seeing such a distant object is equivalent to looking deep into the past. "We were hoping to find a massive starburst galaxy at vast distances, but we did not expect that one would even exist that early in the universe," Riechers says.

To study HFLS3 further, the astronomers zoomed in with several other telescopes. Using the Combined Array for Research in Millimeter-Wave Astronomy (CARMA)—a series of telescope dishes that Caltech helps operate in the Inyo Mountains of California—as well as the Z-Spec instrument on the Caltech Submillimeter Observatory on Mauna Kea in Hawaii, the team was able to study the chemical composition of the galaxy in detail—in particular, the presence of water and carbon monoxide—and measure its distance. The researchers also used the 10-meter telescope at the W. M. Keck Observatory on Mauna Kea to determine to what extent HFLS3 was gravitationally lensed.

This galaxy is the first such object in the HerMES survey to be analyzed in detail. This type of galaxy is rare, the astronomers say, but to determine just how rare, they will pursue more follow-up studies to see if they can find more of them lurking in the HerMES data. These results also hint at what may soon be discovered with larger infrared observatories, such as the new Atacama Large Millimeter/submillimeter Array (ALMA) in Chile and the planned Cerro Chajnantor Atacama Telescope (CCAT), of which Caltech is a partner institution.

The title of the Nature paper is "A Dust-Obscured Massive Maximum-Starburst Galaxy at a Redshift of 6.34." In addition to Riechers, Bock, and Dowell, the other Caltech authors of the paper are visiting associates in physics Matt Bradford, Asantha Cooray, and Hien Nguyen; postdoctoral scholars Carrie Bridge, Attila Kovacs, Joaquin Vieira, Marco Viero, and Michael Zemcov; staff research scientist Eric Murphy; and Jonas Zmuidzinas, the Merle Kingsley Professor of Physics and the Chief Technologist at NASA's Jet Propulsion Laboratory (JPL). There are a total of 64 authors. Bock, Dowell, and Nguyen helped build the Spectral and Photometric Imaging Receiver (SPIRE) instrument on Herschel.

Herschel is a European Space Agency cornerstone mission, with science instruments provided by consortia of European institutes and with important participation by NASA. NASA's Herschel Project Office is based at JPL in Pasadena, California. JPL contributed mission-enabling technology for two of Herschel's three science instruments. The NASA Herschel Science Center, part of the Infrared Processing and Analysis Center at Caltech in Pasadena, supports the U.S. astronomical community. Caltech manages JPL for NASA.

The W. M. Keck Observatory operates the largest, most scientifically productive telescopes on Earth. The two 10-meter optical/infrared telescopes on the summit of Mauna Kea on the island of Hawaii feature a suite of advanced instruments including imagers, multi-object spectrographs, high-resolution spectrographs, integral-field spectroscopy and a world-leading laser guide-star adaptive optics system. The observatory is operated by a private 501(c)(3) nonprofit organization and is a scientific partnership of the California Institute of Technology, the University of California, and NASA.

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Picking Apart Photosynthesis

New insights from Caltech chemists could lead to better catalysts for water splitting

PASADENA, Calif.—Chemists at the California Institute of Technology (Caltech) and the Lawrence Berkeley National Laboratory believe they can now explain one of the remaining mysteries of photosynthesis, the chemical process by which plants convert sunlight into usable energy and generate the oxygen that we breathe. The finding suggests a new way of approaching the design of catalysts that drive the water-splitting reactions of artificial photosynthesis.

"If we want to make systems that can do artificial photosynthesis, it's important that we understand how the system found in nature functions," says Theodor Agapie, an assistant professor of chemistry at Caltech and principal investigator on a paper in the journal Nature Chemistry that describes the new results.

One of the key pieces of biological machinery that enables photosynthesis is a conglomeration of proteins and pigments known as photosystem II. Within that system lies a small cluster of atoms, called the oxygen-evolving complex, where water molecules are split and molecular oxygen is made. Although this oxygen-producing process has been studied extensively, the role that various parts of the cluster play has remained unclear. 

The oxygen-evolving complex performs a reaction that requires the transfer of electrons, making it an example of what is known as a redox, or oxidation-reduction, reaction. The cluster can be described as a "mixed-metal cluster" because in addition to oxygen, it includes two types of metals—one that is redox active, or capable of participating in the transfer of electrons (in this case, manganese), and one that is redox inactive (calcium).

"Since calcium is redox inactive, people have long wondered what role it might play in this cluster," Agapie says.

It has been difficult to solve that mystery in large part because the oxygen-evolving complex is just a cog in the much larger machine that is photosystem II; it is hard to study the smaller piece because there is so much going on with the whole. To get around this, Agapie's graduate student Emily Tsui prepared a series of compounds that are structurally related to the oxygen-evolving complex. She built upon an organic scaffold in a stepwise fashion, first adding three manganese centers and then attaching a fourth metal. By varying that fourth metal to be calcium and then different redox-inactive metals, such as strontium, sodium, yttrium, and zinc, Tsui was able to compare the effects of the metals on the chemical properties of the compound.

"When making mixed-metal clusters, researchers usually mix simple chemical precursors and hope the metals will self-assemble in desired structures," Tsui says. "That makes it hard to control the product. By preparing these clusters in a much more methodical way, we've been able to get just the right structures."

It turns out that the redox-inactive metals affect the way electrons are transferred in such systems. To make molecular oxygen, the manganese atoms must activate the oxygen atoms connected to the metals in the complex. In order to do that, the manganese atoms must first transfer away several electrons. Redox-inactive metals that tug more strongly on the electrons of the oxygen atoms make it more difficult for manganese to do this. But calcium does not draw electrons strongly toward itself. Therefore, it allows the manganese atoms to transfer away electrons and activate the oxygen atoms that go on to make molecular oxygen.

A number of the catalysts that are currently being developed to drive artificial photosynthesis are mixed-metal oxide catalysts. It has again been unclear what role the redox-inactive metals in these mixed catalysts play. The new findings suggest that the redox-inactive metals affect the way the electrons are transferred. "If you pick the right redox-inactive metal, you can tune the reduction potential to bring the reaction to the range where it is favorable," Agapie says. "That means we now have a more rational way of thinking about how to design these sorts of catalysts because we know how much the redox-inactive metal affects the redox chemistry."

The paper in Nature Chemistry is titled "Redox-inactive metals modulate the reduction potential in heterometallic manganese-oxido clusters." Along with Agapie and Tsui, Rosalie Tran and Junko Yano of the Lawrence Berkeley National Laboratory are also coauthors. The work was supported by the Searle Scholars Program, an NSF CAREER award, and the NSF Graduate Research Fellowship Program. X-ray spectroscopy work was supported by the NIH and the DOE Office of Basic Energy Sciences. Synchrotron facilities were provided by the Stanford Synchrotron Radiation Lightsource, operated by the DOE Office of Biological and Environmental Research. 

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Counting White Blood Cells at Home

Caltech engineers lead development of a new portable counter

PASADENA, Calif.—White blood cells, or leukocytes, are the immune system's warriors. So when an infection or disease attacks the body, the system typically responds by sending more white blood cells into the fray. This means that checking the number of these cells is a relatively easy way to detect and monitor such conditions.

Currently, most white blood cell counts are performed with large-scale equipment in central clinical laboratories. If a physician collects blood samples from a patient in the office—usually requiring a full vial of blood for each test—it can take days to get the results. But now engineers at the California Institute of Technology (Caltech), working with a collaborator from the Jerusalem-based company LeukoDx, have developed a portable device to count white blood cells that needs less than a pinprick's worth of blood and takes just minutes to run.

"The white blood cell counts from our new system closely match the results from tests conducted in hospitals and other central clinical settings," says Yu-Chong Tai, professor of electrical engineering and mechanical engineering at Caltech and the project's principal investigator. "This could make point-of-care testing possible for the first time."

Portable white blood cell counters could improve outpatient monitoring of patients with chronic conditions such as leukemia or other cancers. The counters could be used in combination with telemedicine to bring medical care to remote areas. The devices could even enable astronauts to evaluate their long-term exposure to radiation while they are still in space. The researchers describe the work in the April 7 issue of the journal Lab on a Chip.

There are five subtypes of white blood cells, and each serves a different function, which means it's useful to know the count for all of them. In general, lymphocytes use antibodies to attack certain viruses and bacteria; neutrophils are especially good at combating bacteria; eosinophils target parasites and certain infections; monocytes respond to inflammation and replenish white blood cells within bodily tissue; and basophils, the rarest of the subtypes, attack certain parasites.

"If we can give you a quick white blood cell count right in the doctor's office," says Wendian Shi, a graduate student in Tai's lab and lead author of the new paper, "you can know right away if you're dealing with a viral infection or a bacterial infection, and the doctor can prescribe the right medication."

The prototype device is able to count all five subtypes of white blood cells within a sample. It provides an accurate differential of the four major subtypes—lymphocytes, monocytes, eosinophils, and neutrophils. In addition, it could be used to flag an abnormally high level of the fifth subtype, basophils, which are normally too rare (representing less than one percent of all white blood cells) for accurate detection in clinical tests.

The entire new system fits in a small suitcase (12" x 9" x 5") and could easily be made into a handheld device, the engineers say.

A major development reported in the new paper is the creation of a detection assay that uses three dyes to stain white blood cells so that they emit light, or fluoresce, brightly in response to laser light. Blood samples are treated with this dye assay before measurement in the new device. The first dye binds strongly to the DNA found in the nucleus of white blood cells, making it simple to distinguish between white blood cells and the red blood cells that surround and outnumber them. The other two dyes help differentiate between the subtypes.

The heart of the new device is a 50-micrometer-long transparent channel made out of a silicone material with a cross section of only 32 micrometers by 28 micrometers—small enough to ensure that only one white blood cell at a time can flow through the detection region. The stained blood sample flows through this microfluidic channel to the detection region, where it is illuminated with a laser, causing it to fluoresce. The resulting emission of the sample is then split by a mirror into two beams, representing the green and red fluorescence.

Thanks to the dye assay, the white blood cell subtypes emit characteristic amounts of red and green light. Therefore, by determining the intensity of the emissions for each detected cell, the device can generate highly accurate differential white blood cell counts.

Shi says his ultimate goal is to develop a portable device that can help patients living with chronic diseases at home. "For these patients, who struggle to find a balance between their treatment and their normal quality of life, we would like to offer a device that will help them monitor their conditions at home," he says. "It would be nice to limit the number of trips they need to make to the hospital for testing."

The Lab on a Chip paper is titled "Four-part leukocyte differential count based on sheathless microflow cytometer and fluorescent dye assay." In addition to Tai and Shi, the coauthors on the paper are Luke Guo, a graduate student at MIT who worked on the project as an undergraduate student at Caltech, and Harvey Kasdan of LeukoDx Inc. in Jerusalem, Israel. The work was supported by the National Space Biomedical Research Institute under a NASA contract.

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Developing Our Sense of Smell

Caltech biologists pinpoint the origin of olfactory nerve cells

PASADENA, Calif.—When our noses pick up a scent, whether the aroma of a sweet rose or the sweat of a stranger at the gym, two types of sensory neurons are at work in sensing that odor or pheromone. These sensory neurons are particularly interesting because they are the only neurons in our bodies that regenerate throughout adult life—as some of our olfactory neurons die, they are soon replaced by newborns. Just where those neurons come from in the first place has long perplexed developmental biologists.

Previous hypotheses about the origin of these olfactory nerve cells have given credit to embryonic cells that develop into skin or the central nervous system, where ear and eye sensory neurons, respectively, are thought to originate. But biologists at the California Institute of Technology (Caltech) have now found that neural-crest stem cells—multipotent, migratory cells unique to vertebrates that give rise to many structures in the body such as facial bones and smooth muscle—also play a key role in building olfactory sensory neurons in the nose.

"Olfactory neurons have long been thought to be solely derived from a thickened portion of the ectoderm; our results directly refute that concept," says Marianne Bronner, the Albert Billings Ruddock Professor of Biology at Caltech and corresponding author of a paper published in the journal eLIFE on March 19 that outlines the findings.

The two main types of sensory neurons in the olfactory system are ciliated neurons, which detect volatile scents, and microvillous neurons, which usually sense pheromones. Both of these types are found in the tissue lining the inside of the nasal cavity and transmit sensory information to the central nervous system for processing.

In the new study, the researchers showed that during embryonic development, neural-crest stem cells differentiate into the microvillous neurons, which had long been assumed to arise from the same source as the odor-sensing ciliated neurons. Moreover, they demonstrated that different factors are necessary for the development of these two types of neurons. By eliminating a gene called Sox10, they were able to show that formation of microvillous neurons is blocked whereas ciliated neurons are unaffected.

They made this discovery by studying the development of the olfactory system in zebrafish—a useful model organism for developmental biology studies due to the optical clarity of the free-swimming embryo. Understanding the origins of olfactory neurons and the process of neuron formation is important for developing therapeutic applications for conditions like anosmia, or the inability to smell, says Bronner.

"A key question in developmental biology—the extent of neural-crest stem cell contribution to the olfactory system—has been addressed in our paper by multiple lines of experimentation," says Ankur Saxena, a postdoctoral scholar in Bronner's laboratory and lead author of the study. "Olfactory neurons are unique in their renewal capacity across species, so by learning how they form, we may gain insights into how neurons in general can be induced to differentiate or regenerate. That knowledge, in turn, may provide new avenues for pursuing treatment of neurological disorders or injury in humans."

Next, the researchers will examine what other genes, in addition to Sox10, play a role in the process by which neural-crest stem cells differentiate into microvillous neurons. They also plan to look at whether or not neural-crest cells give rise to new microvillous neurons during olfactory regeneration that happens after the embryonic stage of development.

Funding for the research outlined in the eLIFE paper, "Sox10-dependent neural crest origin of olfactory microvillous neurons in zebrafish," was provided by the National Institutes of Health and the Gordon Ross Postdoctoral Fellowship. Brian N. Peng, a former undergraduate student (BS '12) at Caltech, also contributed to the study. A new open-access, high-impact journal, eLIFE is backed by three of the most prestigious biomedical research funders in the world: the Howard Hughes Medical Institute, the Max Planck Society, and the Wellcome Trust. 

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Two Decades of Discoveries

Keck Observatory marks 20th anniversary

Although Keith Matthews was about to make history, he went about his tasks like any others. It was the night of March 16, 1993, nearly 14,000 feet above sea level on Mauna Kea in Hawaii, and he had just installed the first instrument on the brand-new 10-meter telescope at W. M. Keck Observatory. Matthews, who built the instrument—a near-infrared camera, abbreviated NIRC—was set to make the first scientific observations using the newly crowned Biggest Telescope in the World.

This Saturday marks the 20th anniversary of those inaugural observations. Speaking at a symposium on March 7 commemorating the anniversary, Tom Soifer, chair of the Division of Physics, Mathematics and Astronomy, called those initial observations "one of the greatest events in astronomy. It's been a remarkable 20 years of exploration and discovery," he said.

At the time of that first observing run, the telescope had yet to be officially commissioned and wasn't yet optimized, but Matthews—now chief instrument scientist at Caltech—was there to see just what the telescope could do. "Fortunately, it worked right off the bat," he recalls.

The observatory was the culmination of more than a decade of planning, designing, and building made possible by unprecedented financial contributions from the Keck Foundation ($70 million for the first telescope) and by cutting-edge technology. But Matthews didn't feel much reason to jump for joy when he saw that first star, sharp and bright on the computer screen. He was too busy to be excited, he says, and those observations were just another set of steps in a long process that had begun more than a decade prior, when he joined the telescope design team in 1979. Caltech would become an official partner of the observatory in 1985, joining the University of California and the University of Hawaii (NASA would join in 1996).

To be sure, Matthews was happy that everything was working relatively smoothly. But, he says, throughout the whole process of making the telescope and the instrument a reality, there was always something else that he needed to focus on and get done. He was observing alone—a rarity these days—operating on four hours of sleep for roughly nine nights. He slept at 9,000 feet and had to make the drive up the summit into the sun's glare every day. The altitude at the summit made the work even more grueling.

And there were still the inevitable bugs and problems. For one, the Dewar—the container that housed the infrared camera and kept it cold—was leaking liquid helium. Matthews tried everything from rubber cement to glycerol to control the leak. The computers also kept crashing, the monitors going blank one by one. "It was funny," he recalls. "All the screens started to go like a house of cards."

He eventually found stopgap measures to control the leak, and the computers were simply rebooted. The observing run demonstrated that even before the telescope was fully optimized, it was already able to achieve better resolution than the 200-inch Hale Telescope at Palomar Observatory, supplanting the 200-inch as the world's most powerful telescope—a title the 200-inch had held since 1948. A second, identical Keck telescope was built in 1996.

In the two decades since, Keck has become arguably the most prominent and productive observatory in astronomy, helping scientists learn how the universe has evolved since the Big Bang, how galaxies form, and how stars are born. The twin telescopes, Keck I and Keck II, have studied dark matter—the mysterious, unseen stuff that makes up most of the universe's mass—as well as dark energy, the cosmic force that's pushing the universe apart. The telescopes have peered into other planetary systems and revealed insights into the origin of our own solar system. In describing how Keck has surpassed expectations, Caltech's Richard Ellis said at last week's symposium, "Unlike politicians, astronomers deliver much more than they predicted."

The symposium highlighted the fact that Keck has proved indispensible, as a powerful telescope in its own right and as an essential complement to other telescopes. "Keck has been fundamental in establishing partnerships with space telescopes," Ellis said. For example, he has used Keck with the Hubble Space Telescope and the Spitzer Space Telescope to probe some of the most distant galaxies ever observed, revealing a poorly understood period of cosmic history roughly a billion years after the Big Bang. With the help of Keck, Fiona Harrison—a Caltech astronomer and principal investigator of the NuSTAR mission, a space telescope that detects high-energy X rays—discovered bright flares emanating from the supermassive black hole at the center of the galaxy. The flares, she said, could be due to asteroids being ripped apart by the black hole.

And even though NASA's Kepler Space Telescope has been revolutionary in identifying thousands of candidate planets, a ground-based telescope like Keck is needed to verify and characterize those worlds. Caltech's John Johnson, for example, has used Keck to characterize what he says are the most typical kind of planetary system in the galaxy. From his analysis, he estimates that there are at least 100 billion planets in the Milky Way. Keck has also allowed Caltech's Mike Brown to measure detailed spectra of Jupiter's moon Europa, finding evidence that suggests its subsurface ocean may bubble up to its frozen surface.

Of course, none of these discoveries would have been possible without Keck's technological advances. Constructing a telescope as large as Keck using a single mirror would be prohibitively expensive and difficult to engineer. Instead, the Keck telescopes each consist of 36 hexagonal mirrors, forming a total aperture of 10 meters. No one had ever attempted a segmented-mirror telescope before Keck. Ellis was at Cambridge University while the telescope was being developed. "We were looking at this plan with total incredulity," he recalled at the symposium. "The idea of a finely segmented telescope was crazy to us, frankly."

One of the difficulties, for example, was in polishing the mirrors. Because a spherical mirror has rotational symmetry, it's relatively easy to polish. But because each of Keck's segments forms just a part of a parabolic curve, each mirror is asymmetrical, making it near impossible to polish. The solution? Force each segment into a spherical shape. Once polished, the mirror is released and pops back into its original, irregular form.

The telescope is fitted with a suite of instruments that have been constantly upgraded and replaced over the last 20 years—and Caltech has played leading roles with many of those instruments, including NIRC and NIRC2 (the second-generation NIRC) and MOSFIRE (co-led by Caltech's Chuck Steidel), a new spectrometer that was just installed last year. Matthews was also the leader on NIRC2, played a significant role in MOSFIRE, and is now leading the effort on a new instrument, a near-infrared spectrometer called NIRES.

As technology improves, telescopes get bigger and more powerful. Keck's eventual replacement, the Thirty Meter Telescope (TMT), in which Caltech is a partner, won't be ready for at least 10 years. In the meantime, Keck will continue to hold its status as the biggest telescope in the world. And, as Caltech's Judith Cohen pointed out in her symposium talk, even after the TMT is built Keck will remain a useful facility—in much the same way that Palomar Observatory remains productive more than 60 years after it was built. In the last two decades, Keck has had a good run in helping astronomers explore the cosmos—but that run is far from over.

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Marcus Woo
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Bursts of Star Formation in the Early Universe

PASADENA, Calif.—Galaxies have been experiencing vigorous bursts of star formation from much earlier in cosmic history than previously thought, according to new observations by a Caltech-led team.

These so-called starburst galaxies produce stars at a prodigious rate—creating the equivalent of a thousand new suns per year. Now the astronomers have found starbursts that were churning out stars when the universe was just a billion years old. Previously, astronomers didn't know whether galaxies could form stars at such high rates so early in time.

The discovery enables astronomers to study the earliest bursts of star formation and to deepen their understanding of how galaxies formed and evolved. The team describes their findings in a paper being published online on March 13 in the journal Nature and in two others that have been accepted for publication in the Astrophysical Journal.

Shining with the energy of over a hundred trillion suns, these newly discovered galaxies represent what the most massive galaxies in our cosmic neighborhood looked like in their star-making youth. "I find that pretty amazing," says Joaquin Vieira, a postdoctoral scholar at Caltech and leader of the study. "These aren't normal galaxies. They were forming stars at an extraordinary rate when the universe was very young—we were very surprised to find galaxies like this so early in the history of the universe."

The astronomers found dozens of these galaxies with the South Pole Telescope (SPT), a 10-meter dish in Antarctica that surveys the sky in millimeter-wavelength light—which is between radio waves and infrared on the electromagnetic spectrum. The team then took a more detailed look using the new Atacama Large Millimeter Array (ALMA) in Chile's Atacama Desert.

The new observations represent some of ALMA's most significant scientific results yet, Vieira says. "We couldn't have done this without the combination of SPT and ALMA," he adds. "ALMA is so sensitive, it is going to change our view of the universe in many different ways."

The astronomers only used the first 16 of the 66 dishes that will eventually form ALMA, which is already the most powerful telescope ever constructed for observing at millimeter and submillimeter wavelengths.

With ALMA, the astronomers found that more than 30 percent of the starburst galaxies are from a time period just 1.5 billion years after the big bang. Previously, only nine such galaxies were known to exist, and it wasn't clear whether galaxies could produce stars at such high rates so early in cosmic history. Now, with the new discoveries, the number of such galaxies has nearly doubled, providing valuable data that will help other researchers constrain and refine theoretical models of star and galaxy formation in the early universe.

But what's particularly special about the new findings, Vieira says, is that the team determined the cosmic distance to these dusty starburst galaxies by directly analyzing the star-forming dust itself. Previously, astronomers had to rely on a cumbersome combination of indirect optical and radio observations using multiple telescopes to study the galaxies. But because of ALMA's unprecedented sensitivity, Vieira and his colleagues were able make their distance measurements in one step, he says. The newly measured distances are therefore more reliable and provide the cleanest sample yet of these distant galaxies.

The measurements were also made possible because of the unique properties of these objects, the astronomers say. For one, the observed galaxies were selected because they could be gravitationally lensed—a phenomenon predicted by Einstein in which another galaxy in the foreground bends the light from the background galaxy like a magnifying glass. This lensing effect makes background galaxies appear brighter, cutting the amount of telescope time needed to observe them by 100 times.

Secondly, the astronomers took advantage of a fortuitous feature in these galaxies' spectra—which is the rainbow of light they emit—dubbed the "negative K correction." Normally, galaxies appear dimmer the farther away they are—in the same way a lightbulb appears fainter the farther away it is. But it turns out that the expanding universe shifts the spectra in such a way that light in millimeter wavelengths doesn't appear dimmer at greater distances. As a result, the galaxies appear just as bright in these wavelengths no matter how far away they are—like a magic lightbulb that appears just as bright no matter how distant it is.

"To me, these results are really exciting because they confirm the expectation that when ALMA is fully available, it can really allow astronomers to probe star formation all the way up to the edge of the observable universe," says Fred Lo, who, while not a participant in the study, was recently a Moore Distinguished Scholar at Caltech. Lo is a Distinguished Astronomer and Director Emeritus at the National Radio Astronomy Observatory, the North American partner of ALMA.

Additionally, observing the gravitational lensing effect will help astronomers map the dark matter—the mysterious unseen mass that makes up nearly a quarter of the universe—in the foreground galaxies. "Making high-resolution maps of the dark matter is one of the future directions of this work that I think is particularly cool," Vieira says.

These results represent only about a quarter of the total number of sources discovered by Vieira and his colleagues with the SPT, and they anticipate finding additional distant, dusty, starburst galaxies as they continue analyzing their data set. The ultimate goal for astronomers, Lo says, is to observe galaxies at all wavelengths throughout the history of the universe, piecing together the complete story of how galaxies have formed and evolved. So far, astronomers have made much progress in creating computer models and simulations of early galaxy formation, he says. But only with data—such as these new galaxies—will we ever truly piece together cosmic history. "Simulations are simulations," he says. "What really counts is what you see."

In addition to Vieira, the other Caltech authors on the Nature paper are Jamie Bock, professor of physics; Matt Bradford, visiting associate in physics; Martin Lueker-Boden, postdoctoral scholar in physics; Stephen Padin, senior research associate in astrophysics; Erik Shirokoff, a postdoctoral scholar in astrophysics with the Keck Institute for Space Studies; and Zachary Staniszewski, a visitor in physics. There are a total of 70 authors on the paper, which is titled "High-redshift, dusty, starburst galaxies revealed by gravitational lensing." This research was funded by the National Science Foundation, the Kavli Foundation, the Gordon and Betty Moore Foundation, NASA, the Natural Sciences and Engineering Research Council of Canada, the Canadian Research Chairs program, and the Canadian Institute for Advanced Research.

The work to measure the distances to the galaxies is described in the Astrophysical Journal paper "ALMA redshifts of millimeter-selected galaxies from the SPT survey: The redshift distribution of dusty star-forming galaxies," by Axel Weiss of the Max-Planck-Institut für Radioastronomie, and others. The study of the gravitational lensing is described in the Astrophysical Journal paper "ALMA observations of strongly lensed dusty star-forming galaxies," by Yashar Hezaveh of McGill University, and others.

ALMA, an international astronomy facility, is a partnership of Europe, North America, and East Asia in cooperation with the Republic of Chile. ALMA construction and operations are led on behalf of Europe by the European Southern Observatory (ESO) organization, on behalf of North America by the National Radio Astronomy Observatory (NRAO), and on behalf of East Asia by the National Astronomical Observatory of Japan (NAOJ). The Joint ALMA Observatory (JAO) provides the unified leadership and management of the construction, commissioning, and operation of ALMA.

The South Pole Telescope (SPT) is a 10-meter telescope located at the National Science Foundation (NSF) Amundsen-Scott South Pole Station, which lies within one kilometer of the geographic south pole. The SPT is designed to conduct low-noise, high-resolution surveys of the sky at millimeter and submillimeter wavelengths, with the particular design goal of making ultrasensitive measurements of the cosmic microwave background (CMB). The first major survey with the SPT was completed in October 2011 and covers 2,500 square degrees of the southern sky in three millimeter-wave observing bands. This is the deepest large millimeter-wave data set in existence and has already led to many groundbreaking science results, including the first detection of galaxy clusters through their Sunyaev-Zel'dovich effect signature, the most sensitive measurement yet of the small-scale CMB power spectrum, and the discovery of a population of ultrabright, high-redshift, star-forming galaxies. The SPT is funded primarily by the Division of Polar Programs in NSF's Geoscience Directorate. Partial support also is provided by the Kavli Institute for Cosmological Physics (KICP), an NSF-funded Physics Frontier Center; the Kavli Foundation; and the Gordon and Betty Moore Foundation. The SPT collaboration is led by the University of Chicago and includes research groups at Argonne National Laboratory, the California Institute of Technology, Cardiff University, Case Western Reserve University, Harvard University, Ludwig-Maximilians-Universität, the Smithsonian Astrophysical Observatory, McGill University, the University of Arizona, the University of California at Berkeley, the University of California at Davis, the University of Colorado at Boulder, and the University of Michigan, as well as individual scientists at several other institutions, including the European Southern Observatory and the Max-Planck-Institut für Radioastronomie in Bonn, Germany.

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