Berkeley Science Review - Fall 2011

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Fall 2011 Issue 21 sciencereview.berkeley.edu Digitizing the Drawers 36 There’s a map for that Algorithms to ease your commute 28 Innate altruism The psychology of good behavior 20 QB3 Garage Start-ups get a space of their own

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A student-run publication from UC Berkeley covering all things science at Cal. In this issue: mobile technology, brain machine interfaces, bug museums, and much more!

Transcript of Berkeley Science Review - Fall 2011

Page 1: Berkeley Science Review - Fall 2011

Fall 2011 Issue 21

sciencereview.berkeley.edu

Digitizingthe Drawers

36 There’s a map for thatAlgorithms to ease your commute

28 Innate altruismThe psychology of good behavior

20 QB3 GarageStart-ups get a space of their own

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Dear readers,

Welcome to the 21st issue of the Berkeley Science Review. As we saw when this year’s Nobel prizes were awarded last month, UC Berkeley research is perpetually interesting and relevant. (UC Berkeley graduate students are also interesting to Nobel laureates, as Greg Alushin describes (page 6) in his travelogue from the Lindau Meeting.) What we’d like to highlight in this issue is the driving force making science relevant and interest-ing to the public: mathematics and statistics. In our cover story Digitizing the drawers (page 46), Joan Ball relates the efforts of programmers and archivists working with Berkeley’s natural history collections to contextualize and coordinate massive numbers of specimens. In UC Berkeley’s herbaria, there are

360,000 specimens, 14 per Cal undergraduate. The number of cacti in our Botanical Garden alone is equal to the number of professors at UC Berkeley.

Tracking down every miniscule insect specimen in a museum can be a challenge, but at least pinned insects stay in one spot; some researchers on campus are trying to track all of us, every time we leave our houses. Ginger Jui, in There’s a map for that (page 36), gives us a broad view of the algorithmic and statistical analysis behind how we travel, from traffic data on a Google map to cell-phone tracking of road usage and transit time. Robert Gibboni’s Toolbox (page 56) delves into the calculations behind routing algorithms, and explains why simply choosing the faster road is sometimes a poor decision. Researchers hope that, along with taking convenience into account, understanding the costs of commuting in time and energy can drive us to make better choices. Driving more efficiently can make a tangible difference: the typical US household releases 50 tons of carbon dioxide into the atmosphere each year. A 50-ton carbon offset costs $750 on the Chicago Climate Exchange, a kind of stock exchange for greenhouse gases, but of course Berkeley puts a higher value on the environment; to purchase the same amount of carbon dioxide for a campus lab is $1532.

Statistics can also help us analyze the behavior of individuals. In The brain is half full (page 28 ), Azeen Ghorayshi investigates the Greater Good Science Center, an initiative to quantify our better nature, from altruism to collaboration. Even if our capability for good behavior may seem inextricably linked to factors outside of our control, Audrey Chang and Kristina Garfinkel report that anxiety and sleep deprivation are chemically predictable; even itchiness is attributable to a few proteins, described on page 11. Further afield from the Greater Good Science Center, UC Berkeley students are still behaving altruistically, bringing Hepatitis B vaccination to underserved communities in Alameda County, as Sharmistha Majumdar describes (page 4).

Each issue of the BSR requires the coordination of six editors, eighteen authors, seven layout editors, and a statistically significant amount of time and care. I’m overwhelmingly grateful to have Amy Orsborn as my counterpart leading the Layout team, and Mary Grace Lin keeping our resources on track, from finances to enthusiasm. We’re also lucky to have six regular authors (including one combination author and editor) on our blog team, who will keep you updated this semester on posts that tie in with some of the print articles and our second Reader’s Choice Award, where you can vote for the best feature article or brief.

Enjoy the issue,

Allison BerkeEditor in Chief

from the edito rberkeley

Fall 2011 Issue 21

sciencereview.berkeley.edu

Digitizingthe Drawers

Editor in ChiefAllison Berke

Editors Crystal Chaw

Mary Grace LinChris Holdgraf

Sebastien LounisAnna Schneider

Josh Shiode

Art DirectorAmy Orsborn

Layout StaffLeah Anderson

Marek JakubowskiAsako Miyakawa

Helene MoormanValerie O’Shea

Gregory Thomas

Copy EditorGreg Alushin

Managing EditorMary Grace Lin

Web EditorBrian Lambson

Web DirectorChris Holdgraf

PrinterSundance Press

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features

© 2011 Berkeley Science Review. No part of this publication may be reproduced, stored, or transmitted in any form without the express permission of the publishers. Financial assistance for the 2011-2012 academic year was generously provided by the Office of the Vice Chancellor of Research, the UC Berkeley Graduate Assembly (GA), the Associated Students of the University of California (ASUC), and the Eran Karmon Memorial Fund. Berkeley Science Review is not an official publication of the University of California, Berkeley, the ASUC, the GA, or Lawrence Berkeley National Laboratory. The views expressed herein are the views of the writers and not necessarily the views of the aforementioned organizations. All events sponsored by the BSR are wheelchair accessible. For more information email [email protected]. Letters to the editor and story proposals are encouraged and should be emailed to [email protected] or posted to the Berkeley Science Review, 10 Eshleman Hall #4500, Berkeley, CA 94720. Advertisers: contact [email protected] or visit sciencereview.berkeley.edu.

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20 A lab space of one’s ownThe QB3 Garage: an incubator for innovationby Susanne Kassube

28 The brain is half fullThe science behind positive psychologyby Azeen Ghorayshi

36 There’s a map for thatCell phones for a better commuteby Ginger Jui

44 Digitizing the drawersMoving natural history collections onlineby Joan Ball

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COVER: This pinned beetle is one of 6 million invertibrate specimens in UC Berkeley’s Essig Museum of Entomology. The Calbug team is working to build databases to digitize the museum’s collection.

8 Mind over matterBrain machine interfaces come onlineby Samantha Cheung

10 Red eye scienceSleep now, learn laterby Kristina Garfinkel

11 Core issuesModeling the thermodynamic instability of planetary coresby Keith Cheveralls

12 A real head-scratcherThe molecular basis of itchby Nikki Kong

departmentsberkeley

current briefs

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CLOCKWISE FROM TOP-RIGHT: MAREK JAKUBOWSKI; ARTURO NAHUM; ASAKO MIYAKAWA; ERIC FISCHER; ELISABETH FALL; CHARLES DARWIN

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14 A perennial problemDevelopmental deficits stemming from pesticidesby Molly Sharlach

16 One small step for Cal, one giant leap for mankindAdvances in quantum computingby Zlatko Minev

17 Rising above Plateau’s problem250 years of mathematical explorationby Alireza Moharrer

1 From the Editor

4 LabscopesCan that thing fly?by Mica Smith

The frightened brainby Audrey Chang

Hyena gender rolesby Erin Jarvis

Think globally, treat locallyby Sharmistha Majumdar

6 From the fieldby Greg Alushin

52 Book reviewThe Instant PhysicistProfessor Richard A. Muller, illustrated by Joey Manfreby Erin Jarvis

54 Faculty ProfileKaren De ValoisTrue visionaryby Amanda Alvarez

56 ToolboxProbability and statisticsby Robert Gibboni

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Do you tend to “sweat the small stuff?” Chronic anxiety and similar neurological disorders affect over 25 million Americans, and researchers at UC Berkeley have identified two distinct pathways in the brain that can predict an individual’s susceptibility to anxiety. In this col-

laborative study between the Bishop lab at UC Berkeley and colleagues at Cambridge University, changes in blood flow to the brain were measured while subjects viewed a computer-generated

image of a person in a room just before a loud scream is heard. For some trials, the virtual figure in the room moves to cover its ears just before the scream, while in other trials the

gesture does not predict the sound, keeping subjects in a perpetual state of anticipation. Some participants with abnormal fear responses displayed a stronger reaction to

the virtual figure covering its ears—the anticipation of the loud scream led to overactivity in the amygdala region of the brain, which is known to process emotional memories. Others showed less activation in the ventral prefrontal cortex, a region responsible for decreasing the fear response. These are two separate mechanisms, but failure in either one results in a heightened fear response. This model of anxiety—activation instead of regulation—can better guide targeted therapies for anxiety disorders in the future. By understanding which mechanism is the source of an increased fear response, the success of different treatments can be better predicted.

The frightened brain

The giant hummingbird, Patagona gigas, native to the Andes, is an over-sized cousin of the Anna’s hummingbird beloved in North American backyards. It weighs about 20 grams, as much as a toothbrush, which

is twice as much as the next largest of more than 300 known hummingbird species. Professor Robert Dudley and María José Fernández of UC Berkeley’s integrative biology department analyzed the flight mechanics and metabo-lism of Patagona gigas in search of an explanation for its extreme body size.

“Muscle efficiency in general tends to be greater for larger things,” said Dudley, who wondered whether Patagona gigas evolved to take advantage of more effective energy use in the high elevation of the Chilean Altiplano. However, the giant hummingbird’s metabolic rate relative to its size cor-relates with data Dudley’s group collected for a number of smaller species. So if the giant hummingbird doesn’t expend more energy to sustain itself in flight, why haven’t hummingbirds evolved to grow even larger? Dudley cites the example of the nectar feeding bat, another vertebrate species that hovers, and can weigh up to 40 grams. “The wing design is very different,” says Dudley. “Bat wings connect to the hind legs, so they’ve got about twice the wing area. Depending on the aerodynamic mechanisms involved, the motor may be irrelevant: it’s your ability to convert that to aerodynamic force.” He speculates that the counterbalance between increasing wingspan and decreasing wingbeat frequency may place an upper limit on body size, which is represented by Patagona gigas. Though the results show that the hummingbird’s characteristically high metabolism is unaffected by size, it’ll be awhile on the evolutionary timeline before we see birds as big as falcons hovering at our feeders.

Can that thing fly?

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Approximately 1.25 million Americans are chronically infected with hepatitis B, a blood-borne, sexually transmitted virus that causes severe liver diseases like cancer and cirrhosis. Of this group, over 50% are Asian and Pacific Islanders (API), many of whom live in California. However, such high numbers aren’t due to a lack of medical technology. “What is ironic is that a vaccine has been available for over twenty

years!” muses Adele Feng, a UC Berkeley undergraduate and the Director of the campus-based Hep B Project, a volunteer organization founded in June 2009 to address the lack of hepatitis B services in Alameda County, California. Working with other community partners, Feng’s group has been involved in organizing free hepatitis B screenings and vaccinations as well as spreading awareness among low-income Asian immigrant com-munities, one of the most at-risk populations in Alameda County. The county lacks a central database with reliable information about the statuses of local hepatitis B patients, resulting in an inefficient allocation of resources, outreach, and services. After two years in the community, the Hep B Project realized that they needed to expand beyond their motto of “Educate, Screen, Vaccinate” and start addressing this problem. The organization recently embarked on a project to integrate existing databases of non-sensitive patient data from local organizations and the Alameda County Public Health Department. With this more comprehensive dataset, they hope to create maps of hepatitis B prevalence and at-risk populations in the Bay Area using Geographic Information System (GIS) technology. This effort was a recent winner at the Big Ideas contest conducted by CITRIS (Center for Information Technology Research in the Interest of Society) at UC Berkeley. The group’s proposal included building an easy-to-navigate, user-friendly interface that allows users to look at overlapping demographic factors such as ethnicity, age, and infection distribution on one map. Eventually, public health officials and community organizations should be able to identify and predict areas of greatest need for preventative and disease-management services, as well as target at-risk and affected populations in a more efficient and cost-effective manner.

Think globally, treat locally

Spotted hyenas are a curious species. They are one of the very few mammals that maintain complicated social hierarchies within a female-dominated society, and are one of

the only non-primate species that can recognize animal relationships in which they are not directly involved. And, to the surprise of many, there is a clan of 26 hyenas living in the Berkeley hills. Before you start questioning the safety of your evening jogs above campus, rest assured that the hyenas are part of a captive breeding colony housed at the Field Station for the Study of Behavior, Ecology, and Reproduction (FSSBER), maintained by the University of California, Berkeley. UC Berkeley researchers Frederic Theunissen (Professor of Psychology), Mary Weldele (psychology and integrative biology), Aaron Koralek (graduate student at the Helen Wills Neuroscience Institute), and Stephen Glickman (Professor of Psychology and Integrative Biology) observed the hyena colony to decipher a distinctive yet cryptic hyena trait: the giggle, and its meaning in hyena society. Hyena social status is maintained by a complicated social network of coalitions and alliances, which requires an intricate system of communication. Hyenas communicate visually, chemically, and, as a major backdrop to the nightly chorus of the African Savannah, acoustically. The quintessential hyena call is the giggle—a high-pitched sound emitted in bouts that sounds like laughter. “The function of the giggle call is actually very poorly understood,” says Aaron Koralek. “This was some of the first work looking at if [the hyena giggle] could potentially serve a social function.” The hyena giggle is most frequently emitted by a subordinate competing over a carcass with a dominant member, and previous observations suggested that the giggle was a subordinate call. Research further suggests that the giggle is a frustrated response to wanting something and not getting it: another good reason not to tease a hyena.

Hyena gender roles

Chronic Hepatitis B cases in SF area

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My advisor, molecular and cell biol-ogy professor Eva Nogales, burst into the room: “Greg, I need to

speak with you right now.” Spurred from my mild Friday afternoon torpor, I felt a momen-tary panic. Once we were out in the hallway, though, instead of harsh words she offered me an opportunity: the chance to apply to the Lindau Meeting, a unique conference where Nobel laureates and young scientists from around the world come together for a week of scientific discourse. There was, however, a catch. Berkeley was forwarding the first two applications it received to the reviewing committee, and one had already been submitted. I had one hour to write an essay and prepare my C.V. so the materials and a recommendation could be submitted by the end of the day. Confident that such frantic last minute efforts would be sub-par, I cranked out an application and promptly forgot about the whole thing. To my amaze-ment, a few weeks later I was informed that I had made it to the next stage in the selection

process. Then the final word came: I was in, one of 567 winners from a pool of 20,000 applicants heading to Lindau.

Only many months later did I come to appreciate the gravity of the event. Instead of a summer prize for lucky graduate students, the meetings began as an effort to reintegrate Germany with the international scientific community after World War II. Two doctors from Lindau, a picturesque medieval town on Lake Constance in southern Germany, persuaded the local government to host an international conference and boost its visibility by specifically inviting Nobel laureates. They also won the backing of a local nobleman, Count Lennart Bernadotte, who became the driving organizational force.The first meeting, held in 1951, was small but successful. It focused on reestablishing ties between expatriate German scientists and those who had remained during the war, including Nobel laureates from both categories. In 1954, young researchers were invited for the first time, beginning a shift in

focus toward laureates mentoring students. An increasing international presence steadily gathered, and today the participants hail from more than 70 countries. Nevertheless, the event maintains strong ties to its origins: Count Bernadotte’s daughter, Countess Bettina Bernadotte, is the reigning president of the Lindau council.

Living up to its varied history, this year’s conference see-sawed between prestigious international discourse and truly local flavor. The theme of the conference was global health, and the opening ceremony featured Bill Gates engaging in a panel discussion with two young scientists and Nobel laureate Ada Yonath about how best to confront the health challenges of the developing world. In contrast, the Elite Bavarian Network hosted an evening session with local officials who tried to sell the audience on the joys of living and working in the vicinity and, bizarrely enough, lederhosen-clad dancers. Most days featured plenary lectures by several Nobel laureates in the morning, which varied

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Greg Alushin (center) talking with Chemistry nobel laureate Robert Huber (right) along with a student from Indonesia (left).

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widely, from the extremely technical, such as Ei-ichi Negishi’s detailed explanation of the reaction mechanisms of palladium-catalyzed carbon-carbon bond formation, to personal history and anecdotes, such as Oliver Smithies’s declaration that, “Out of laziness, I invented gel electrophoresis.” Each of the speakers hosted a smaller session in the afternoon, which were closest to what I had imagined I would experience: an intimate, intergenerational conversation between some of science’s leading lights and those who hope to follow in their footsteps.

As I navigated the whirlwind of talks, discussion panels, and round-the-clock net-working with some of the most intense young scientists I have encountered, it occurred to me that the meetings were, once again, evolv-ing into a new stage. With high-powered VIPs and international delegations, including government officials, vying for the attention of the laureates, the Lindau Meetings have gone big. Of course, that means there are power lunches, invitation only. At one such event, laureate Bert Sakmann told me that when he was a medical student in Germany in the late sixties and early seventies he and his friends used to simply drive over to the meeting every year to hang out and chat with the laureates. Now, laureates are whisked from event to event in private cars provided by Audi, one of many corporate sponsors. Journalists and bloggers cover every lecture, and Nature even sends a team to film a docu-mentary. The scope is changing, from strictly promoting dialogue between the “best” sci-entists and the “best” students, a concept that, while wonderful for the participants, is surely elitist, to displaying that dialogue, and all the hope and excitement that it generates, to a world that is hungry for inspiration.

This shift in character implicitly raises the question, a central thread running through the conference, of what scientists should actually be doing. With their choice of global health as a theme, the organizers are clearly on the side of science for society, that is, scientists creating and disseminat-ing knowledge for a better world. Sessions

were geared towards getting young researchers interested in working on neglected dis-eases and problems whose solutions would benefit all of humanity, not just rich, technologically advanced nations. Many of the laure-ates, however, did not jive with this message, making it clear that they had simply worked on a problem they found personally interesting without thinking about what impacts it might have, or had made their prize-winning discoveries by accident, fol-lowing up on an unexpected observation. A few laureates, particularly Sir Harold Kroto of bucky-ball fame, advanced a similar argu-ment about technological developments; many follow basic science discover-ies made by scientists in seemingly unrelated fields, performing research for its own sake.

Throughout my own scientific journey thus far, I have been partial to the trickle-down model of societal benefits from pure science, echoed by many of the laureates. However, my experience at Lindau did get me thinking about working on a problem with a more explicit goal of improving the world while also follow-ing my curiosity. And, if I get extraordinarily lucky, it might earn me a second trip to Lindau.

Greg Alushin is a graduate student in biophysics.

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Mind over matterBrain–machine interfaces come onlinePossessing the power to control artificial devices with thoughts alone seems straight out of a science-fiction movie. However, with the help of a team of neural pros-thetics researchers at UC Berkeley, this idea is moving closer to reality. Although common sci-fi abilities such as the super-human strength to destroy buildings or the ability to download martial art skills from a computer are still the stuff of fiction, there is one fantastic ability that the newly-formed Center for Neural Engineering and Prostheses (CNEP) would like to make a reality: giving paralyzed patients control of prosthetic devices using only their thoughts, allowing them to perform simple daily tasks independently.

The CNEP, co-directed by Professor Jose Carmena from UC Berkeley and Professor Edward Chang from UC San Francisco, is a collaborative effort to develop neural prosthetic devices, drawing from the efforts of neuroscientists, neurosurgeons, and engi-neers from both universities (see “Plugging back in,” BSR Fall 2009). These devices will prove particularly useful for patients with neurological disorders that impair senso-rimotor and linguistic ability, such as stroke, spinal cord injury, and amputations. The center hopes to develop technologies that can restore sensations, motor movement, and speech by relaying neural communication between the brain and external devices.

The concept of such devices is not novel; for decades neural prosthetics have performed a range of services such as helping the deaf hear or treating symptoms of neu-rological disorders like Parkinson’s disease. Available technologies work by stimulating relevant sensory nerves or regions of the

brain and have paved the path for more neural prosthetic research. However, they are not sophisticated enough to interpret and enact the intentions of their users. Brain-Machine Interface (BMI) technology consists of components that allow robotic devices to directly communicate with the user’s brain. These include a sensor that reads neural signals signifying the patient’s intentions, a processor that decodes the user’s intention into an understandable task for the prosthetic device, and the prosthetic device that carries out the intended task. The goal, according to Carmena, is to “allow a patient to have naturalistic control of a prosthetic device—to feel the prosthetic arm as part of the body.”

In addition to the engineering chal-lenges of developing “extremely small, high bandwidth, ultra-low power implantable devices,” says Carmena, there is a challenge involving movement replication. At the core of this problem is the fact that motor actions in our everyday life are far more complicated than we assume. Even the seemingly simple task of grabbing an object involves calcu-lated and continuously refined movement. To properly navigate the hand toward an object in three-dimensional space, the cor-rect muscles must be activated to move the hand toward its goal. Meanwhile, off-course movement must be detected and corrected through cross-talk between motor regions of the brain with visual and spatial feedback to allow trajectory correction toward the object. Moreover, there are many possible ways for us to move our limbs to get to our endpoint. For us, the task appears simple because of neural networks that were fine-tuned as we learned how to utilize our limbs to achieve

our intended task. “Achieving the same naturalistic capability with a BMI becomes much more difficult,” says Carmena.

Regardless of the challenges, the neural prosthetic field is flourishing as technologi-cal barriers are broken. Carmena’s previous work in macaque monkeys revealed the feasi-bility of neural prosthetics by demonstrating that the monkeys could learn how to use a robotic arm with brain signals that are normally involved in motor control. Another important step for BMI research came from a study at Brown University where devices similar to those used in macaques were implanted in the brain of a quadriplegic human patient. Impressively, BMI implanta-tion in the region of the brain that controls motor movement gave the patient the ability to move a computer cursor around a screen.

In addition to enabling people to control computers, CNEP researchers also hope that their neural interfaces will help us under-stand how brains adapt to these devices. “You might not need a full understanding of how we control our body to get the patient’s brain to control the prosthetic device,” mentions Carmena, “but it will facilitate us in getting there sooner.” By training primates with implanted BMIs to do behavioral movement tasks and simultaneously observing proper-ties of neurons in the motor region of the brain, CNEP researchers were able to deter-mine that there are reversible, large-scale changes in these motor areas. Interestingly, the amount of change, both structurally and functionally, was correlated with involve-ment in controlling the BMI. The study also suggested the formation of a prosthetic motor memory, because the monkeys tested do not have to relearn how to use the BMI

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on a daily basis. According to Carmena, the brain establishes “in neural space, a network to control this device as if it were part of its own body.”

In the short period since its launch in December 2010, CNEP has made impressive progress. Nevertheless, many challenges remain. For example, control-ling a computer cursor is not the same as controlling a robotic arm to do an array of daily tasks. “Controlling a multi degree-of-freedom (DOF) robotic arm to inter-act with the real world for tasks of daily living is sig-nificantly more complicated than a 2-DOF computer cursor,” says Carmena. Still, CNEP is moving closer to developing patient-ready BMI technology. Although the primary goal is to help paralyzed individuals perform daily tasks independently, relieving their families of the cost and time of aided living, CNEP also hopes to obtain a better understanding of neural tasks such as processing sensory information, executing movements, and learning to adapt to novel external sys-tems. Although CNEP scientists still have a way to go before restoring or providing thought-controlled motor tasks to patients with neural deficits—they are beginning to understand more of the complex properties of the brain, one step at a time.

Samantha Cheung is a graduate student in molecular and cell biology.AU

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Red eye scienceSleep now, learn later

Why are we alert at some times of the day and not others? Why are we hungry in the morning? Why do we (and other diurnal creatures) become sleepy when darkness encroaches? It is not possible to be awake and asleep at the same time: something favors specific behaviors at specific times. Psychologists and biologists have long been attempting to define what exactly drives the timing of animal behavior and, more recently, what happens when these adaptive rhythms are disrupted. Over the past 300 years, scientists have discovered that the mechanisms controlling our behaviors are internal; we all have daily (circadian) and annual biological clocks. The circadian clock is generated at the single-cell level through control of the expression of specific genes and their protein products.

Biological rhythms use chemical signals to ensure that throughout the day our bodily processes and behavior follow a specific pat-tern that is coordinated with the local time. For example, a surge of cortisol peaks in the morning and encourages us to wake up, and a rise of melatonin later follows to induce

sleepiness. In mammals, these daily signals are coordinated and sustained by a specific region of the brain, the suprachiasmatic nucleus (SCN). Information about the time of day is relayed from the light-sensitive cells in the retina of the eye and travels down the retinohypothalamic tract to reach the SCN. The SCN uses the input of light and darkness to synchronize every cell in our bodies with the external environment, influencing our behavior. This results in rhythms in gene expression that form approximately 24-hour cycles that are ubiquitous among living organisms. Yet humans have developed modern rituals that interfere with our inter-nal systems. Frequent traveling, alternating work schedules, fluctuating sleeping patterns, and other exogenous factors that humans face can disrupt both the phase relationships between different hormones and the relation-ship between hormones and time.

By mimicking jet lag in hamsters, UC Berkeley neuroendocrinologists Lance Kriegsfeld and Erin Gibson, a graduate student in Kriegsfeld’s lab, have recently conducted the first controlled study on how circadian disruption affects brain function in general, and memory in particular. Twice

a week for one month, researchers subjected female hamsters to six-hour time shifts in their light/dark cycles, equivalent to the shift one would experience from a New York-to-Paris flight. The hamsters were given a learn-ing and memory task before and immediately after the time shifts to assess the effects of jet lag on cognitive function. As anticipated, the hamsters performed poorly at learning new tasks during the jet lag weeks. Surprisingly, when the hamsters were re-tested 30 days later—after they had returned to their regu-lar day-night cycles—the hamsters continued to display prolonged memory deficits. “Most people assume the reason they cannot learn new information at the time of feeling jet-lagged is because they are just not feeling well. This study suggests that this may not be due to simply feeling tired, but because you are disrupting specific bodily processes that are necessary for the brain to form new memories,” says Kriegsfeld.

Those that have traveled to a new time zone are familiar with the feelings associ-ated with jet lag. The feeling of trying to stay awake while your body thinks it’s time to sleep, the feeling of not being hungry and then suddenly having a ferocious appetite. The hormones we release when our bodily states become incongruent with environ-

mental cues cause most of these symptoms. Previous studies have shown that

animals often respond to circadian disruption by releasing stress hor-mones such as cortisol inan attempt to regain their allostatic balance (stability achieved by altering behavior or physiology). To ensure that the findings of Kriegsfield’s study were not caused by changes in hormone levels, one group of the hamsters had their adrenal glands and ovaries removed and received supplements to main-tain normal levels of cortisol and estrogen. Although the amount of hormones circulating through their bodies was controlled, the hamsters performed just

as poorly on their tasks. If poor performance

cannot be blamed on feeling fatigued or jet-lagged, something

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independent of hormonal response caused the hamsters to be less efficient at forming new memories. It appears that circadian dis-ruption directly impairs cognitive function without being mediated by stress, and that impairment persists long after returning to a regular cycle.

What caused the hamsters to experi-ence cognitive deficits? Human studies have shown that jet lag increases both atrophy in the temporal lobe of the brain and deficits in learning and memory. Kriegsfeld and Gibson were the first to look at the direct relationship between jet lag and cognitive dysfunction, and did so by examining whether neurogene-sis—the birth and maturation of neurons—in the brain is associated with the learning and memory impairments seen in the hamsters.

“The past studies are all correlational. To find out what is really going on, the first step is looking to see if fewer neurons are being born and incorporated in the hippocampus, the memory center of the brain, because this is critical for learning and retaining new information,” says Kriegsfeld. Neurogenesis was monitored and, sure enough, the find-ings were in agreement with performance on the learning and memory tasks: neurogenesis in the jet-lagged hamsters decreased by 50%. Jet lag seems to impair cognitive function, likely by affecting neurogenesis.

While Kriegsfeld’s study shows that cir-cadian disruption has pronounced negative effects on the brain, the root cause behind the reduction of neurogenesis has yet to be elucidated. Future studies are planned to investigate the mechanism of this reduction, and to see if neuronal death (as opposed to birth and maturation) is impacted as well. The findings of this study emphasize the long-term detrimental consequences that arise when individuals partake in f luctu-ating schedules or poor sleeping habits. Unfortunately, these fluctuations are often inevitable, and we are forced to disrupt our circadian rhythms. Kriegsfeld advises the use of melatonin pills to help properly adjust to phase changes; allowing a one-day recovery for every hour of phase shift may also help avoid problems associated with jet lag.

Kristina Garfinkel is an undergraduate student in psychology.

Core issuesModeling the thermodynamic instability of planetary cores

The interior of a planet is an unimaginably inhospitable place. Pressures reach millions of times those on the surface of the earth, and temperatures far exceed any which we experience. At these extreme conditions, strange things happen. Rocks flow like fluids, water freezes into exotic kinds of ice-like solids, and hydrogen begins to conduct electricity.

Although the interior of the Earth is relatively well understood, the interiors of the gas giants in our solar system—Jupiter and Saturn—are nearly complete enigmas. Unlike Earth, these planets lack a well-defined solid surface. Instead, the atmo-sphere of a gas giant simply becomes denser and more liquid-like towards the planet’s center until, in effect, it becomes an ocean. Deep beneath this liquid ocean, or mantle, scientists believe that gas giants have cores of rock and ice. Little is known about these obscured cores, and understanding their basic properties—how large they are, how they form, or how they interact with the surrounding mantle—remains one of the greatest mysteries of the gas giants.

In a new paper, Burkhard Militzer and his group in Berkeley’s earth and planetary sciences department have provided evidence for a startling new possibility about the core of our solar system’s largest gas giant, Jupiter. Using computer simulations and information about the composition of Jupiter’s interior, they show that Jupiter’s core is likely unstable and is dissolving into the planet’s mantle of liquid hydrogen. Eventually, their results suggest, it may disappear entirely.

While others have proposed the pos-sibility that the cores of Jupiter and other gas giants are unstable, the plausibility of this hypothesis has remained untested because replicating Jupiter’s intense temperatures and pressures here on Earth is extremely difficult. “It’s not obvious whether the core will dissolve,” says Militizer. “We ask the best high-pressure physicists, and they don’t know. The pressures are obscenely high, and there are no experiments that address this question.”

Whether the core is stable or whether it dissolves depends upon a competition between pressure and temperature. On the one hand, the extreme pressures inside Jupiter should generate forces that stabilize the core and combat erosion. On the other hand, the high temperatures in the core tend to favor disordered states in which the core dissolves and mixes with the mantle. “If temperature wins, then it’s like sugar in coffee, and the core erodes,” Militzer explains, referring to the fact that higher temperatures make it easier for solids to dissolve into their liquid surroundings.

Because experiments cannot replicate the conditions within Jupiter, Militzer and a postdoctoral fellow, Hugh Wilson, turned to computer simulations to test the core erosion hypothesis. While Jupiter’s core consists of both rock and ice, the pressures are so great that the ice, which is less dense than the rock, is squeezed from the rock and forms a layer surrounding it, much as the oil and vinegar in salad dressing separate into layers. If Jupiter’s mantle of liquid hydrogen could dissolve this layer of ice, then the icy outer layer of the core would be unstable.

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An illustration of the basic structure of Jupiter’s interior. A mantle of liquid hydrogen, in both metallic and molecular forms, surrounds the core. Militzer’s work suggests that the icy outer layer of the core (not shown) is dissolving into the surrounding liquid hydrogen.

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Using techniques from statistical mechanics, Wilson and Militzer wrote simulations to calculate whether the ice would be more thermodynamically stable if it were dissolved in the liquid hydrogen. They found that the dissolved state was more favorable, just as sugar in coffee is more thermodynamically stable dissolved than as solid crystals. This result implies that the interface between the hydrogen and the icy core is unstable and that the mantle of liquid hydrogen is, in effect, melting the ice.

Militzer is particularly excited about this result because a new NASA mission to Jupiter, launched this August, will offer an unprecedented opportunity to directly test his hypothesis. The satellite, called Juno, will reach Jupiter in the year 2016 and will study the planet in greater detail than ever before. Of interest to Militzer are the measurements that Juno will make of the planet’s gravitational field, because they will allow scientists to precisely calculate the size of the core.

“If they find a giant core, then this

process will either not exist or be really slow,” says Militzer. But a smaller core—one smaller than predicted by theories of planet forma-tion—would be strong evidence in favor of core erosion. Indeed, a very small core would indicate that even the rock beneath the ice has eroded. Militzer is currently testing that possibility by running simulations to test whether the hydrogen mantle would also dissolve the rock at the center of Jupiter’s core.

For all the exotic forms of matter and complex simulations involved, the effects of the core instability predicted by Militzer’s work are subtle and only observable by the kind of precise gravitational measurements the Juno mission will generate. However, Militzer believes that if core erosion is occur-ring in Jupiter, then it probably also occurs in many other Jupiter-sized gas giants and, indeed, is likely a fundamental feature of planetary dynamics.

Keith Cheveralls is a graduate student in biophysics.

An artist’s conception of Juno in orbit around Jupiter. Launched in August, the satellite will reach Jupiter in 2016 and will make precise measurements of Jupiter’s gravitational field, allowing scientists to calculate the size of Jupiter’s core. These calculations will rigorously test Militzer’s hypothesis that the core of the planet is eroding.

A real head-scratcherThe molecular basis of itch

Why do you itch? Yes, yes, that rash, those hives, sure. But what is that sensation? Why does scratching sometimes increase pain but reduce itch? And why are drugs that treat the itch from a mosquito bite powerless against the itch that accompanies an effective and widely-used malaria treatment? The first step in answering these questions is to map the molecular route between your brain and the stimuli causing pain or itch. Discoveries at this molecular level are crucial for drug design and medical therapy. UC Berkeley molecular and cell biology professor Diana Bautista and her colleagues are exploring the molecules that function in the neural pathways behind itch and pain. Her research may someday mean that we can put all that nasty scratching behind us.

The sensation of itch, or pruritus, has traditionally been viewed as a milder form of pain, suggesting that both sensations are mediated by common chemical signals and pathways. Recent evidence challenges this long-standing model by supporting the idea that pain and itch are distinct sensations mediated by separate groups of neurons, or lines of communication to the brain. This theory better explains why vigorous scratch-ing, which produces mild pain, can have an inhibitory effect on itch; chemicals released by the “pain line” can mask the effects of the “itch line.” In a recent paper published in Nature Neuroscience, the Bautista lab reports that a particular neural ion channel called TRPA1 may bridge these two theories and provide a long-sought-after target for treat-ing a variety of pains and itches.

TRPA1 is something of a gatekeeper in pain and itch signaling, acting in response to both pain and itch stimuli while residing in a subset of the neurons associated with itch. As an ion channel, TRPA1 operates at the cell membrane to activate neuronal firing in response to different signals. In biological signaling, a stimulus activates a receptor (molecule A) that results in a signal to molecule B, which in turn activates C and so on. Molecules B and C are defined as

“downstream” of A. Receptors are often very specific, binding their activating molecules N

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like a lock and key. Often, a single event like a mosquito bite results in a barrage of different molecules that activate a variety of signaling pathways. “Most itch conditions involve more than one activating molecule,” says Sarah Wilson, a graduate student in the Department of Molecular and Cell Biology at UC Berkeley and the lead author on the paper. “Blocking one receptor [upstream] might inhibit some of the mosquito-bite itch, for example, but other itch signals can still get through.” So, targeting a single receptor is ineffective at stopping the wide variety of stimuli that can cause itch and pain. This is where TRPA1 comes in. In the pain and itch-signaling pathway, TRPA1 is found downstream of the receptors that initially signal irritation to the body. So when a mosquito bites, the sensation is not imme-diately relayed by TRPA1. This positioning is important because it means that many dif-ferent itch and pain-causing chemicals all go through one gatekeeper, TRPA1. “Inhibiting TRPA1 will block many more of the signals relayed by a single bug bite,” says Wilson.

The Bautista lab team and other neurobiologists initially identified TRPA1 as a pain sensor, but they noticed that it is expressed in the dorsal root ganglion (DRG)—a fraction of neurons that also sense itch. They tested whether the TRPA1 ion channel plays a role in mediating itch using multiple techniques. First, they genetically engineered mice to lack TRPA1. Then, they isolated their DRG neurons and treated them with itch-inducing compounds: the malaria drug chloroquine (CQ) and an endogenous pruritogen (something produced naturally in your body to induce itch), BAM peptide. As com-pared to normal DRG neurons, those that

lacked TRPA1 failed to activate in response to the compounds. To confirm this result, itch-inducing compounds were injected into mice lacking TRPA1 and their behavior was compared with normal mice. The normal animals responded to the injection by distinct, quantifiable scratching behaviors. However, mice lacking TRPA1 outwardly showed decreased responses to both com-pounds; when injected with them, the engi-neered mice did not scratch as furiously as their normal counterparts.

The Bautista lab’s discovery that TRPA1 acts not only as a pain sensor but also as an itch relay has far-reaching implications for drug design. Although treatments for the histamine-mediated mosquito-bite itch already exist in the form of anti-histamines, these drugs are like fighting only one platoon of an enemy’s army while being attacked on multiple fronts. TRPA1 might be the key to a strategy for cutting off the enemy’s supply route and thus crippling all of its forces. “That’s why anti-histamines don’t always work,” says Bautista. “The same cells that release histamine also release BAM peptides, among many other compounds.” Furthermore, itch

sensations associated with chronic illnesses such as liver disease, atopic dermatitis, or side effects of CQ are all unaffected by anti-histamines. The Bautista lab’s discovery has the potential to make finding the specific pathways behind these chronic itch condi-tions unnecessary.

TRPA1 appears to be a specific and important target for drug design. Currently, the Bautista lab is working with Hydra Biosciences to test TRP channel inhibitors in mouse models that exhibit chronic itch. Encouragingly, inhibiting TRPA1 activity reduces both CQ and BAM-induced itch responses in mice, according to Bautista. In the future, they hope to have effective and specific treatments against chronic, intractable itch.

Nikki Kong is a graduate student in molecular and cell biology.

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A perennial problemDevelopmental defects stemming from pesticidesAnyone who has spent time around small children knows that they are constantly experimenting: they are compelled to taste, smell, touch, and sometimes break, almost every object they come across in order to find out what it is and how it works. These are all normal behaviors, and it has long been understood that children’s natural curiosity is vital to their cognitive, social, and emotional development. However, the same curiosity that nurtures young minds can also put them in danger, especially when it comes to potentially toxic chemicals in the environment. Moreover, the undeveloped nature of fetuses and infants leaves them

particularly vulnerable to the outside world. By the 1990s, researchers in the field

of environmental health had become more aware of the unique effects that chemical exposures can have on children, prompting authorities to create programs and rules designed to protect our carefree young-sters. Spurred by an executive order from President Clinton in 1997, the Environmental Protection Agency (EPA) and the Department of Health & Human Services launched eight Children’s Environmental Health Research Centers around the country. The goals of these research centers are to broaden our understanding of the relationship between environmental exposures and child health, and to facilitate the translation of basic research into new strategies for interven-tion and prevention. Focusing largely on the effects of pollutants such as pesticides,

each center is a community–university part-nership that fosters collaborations among academic researchers, health professionals, community leaders, and policy makers.

One of these centers was established by UC Berkeley in the Salinas Valley, an agricultural area south of San Francisco whose population is mainly low-income and Mexican-American. The first major research study on this population was led by Brenda Eskenazi, a professor at the School of Public Health, and was titled “The Center for the Health Assessment of Mothers and Children of Salinas,” or CHAMACOS (which means “little children” in Mexican Spanish). The center enrolled a cohort of six hundred pregnant women with the goal of observ-ing the development of their children from before birth through age twelve. To date, the group has collected data on everything from

A common sight in the Salinas Valley: strawberries being sprayed with pesticides. Dr. Brenda Eskenazi and colleagues found that pesticides such as organophosphates can be harmful to developing fetuses even at low exposure levels. LO

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the children’s environmental exposures to their growth and development, even detail-ing their genetic backgrounds.

Of particular interest to CHAMACOS is a harmful class of chemicals known as organophosphate (OP) pesticides. OPs are widely used in agriculture, especially on commonly eaten fruits like strawberries and grapes; until 2003, they were also autho-rized for both indoor and outdoor home use. Their effects on the human body at low levels are not well understood, but at high doses, organophosphates inhibit acetylcho-linesterase, an enzyme that breaks down the neurotransmitter acetylcholine (ACh). ACh is a chemical that stimulates brain activity, and without acetylcholinesterase to break it down, excess levels of ACh cause uncontrol-lable excitation in the brain. Bradley Voytek, a post-doctoral researcher at the University of California, San Francisco, explains the problems caused by chemicals like OPs:

“Acetylcholinesterase inhibitors are a class of drugs that are found naturally in snake venoms and plant poisons—they increase acetylcholine available to neurons, which slows the heart rate and contracts muscles. Too much of it can obviously be a bad thing.” Thus, increased levels of OPs can lead to a wide variety of neurological problems. In fact, they are so effective at harming human beings that they were developed as chemical weapons (such as sarin) by the Nazis during World War II, and were infamously used in a 1995 terrorist attack on the Tokyo subway.

While most earlier studies of OP expo-sure have focused on agricultural workers exposed to high doses, the CHAMACOS study is concerned with the lifelong, lower doses that the general population receives, particularly from pre-birth to age seven. As Professor Eskenazi explained, “Before we did these studies it was well known that pesticide poisonings occur in children—that’s high-dose exposure. Our question was, ‘What happens with low-dose [exposure] during the course of pregnancy—during fetal devel-opment, when the fetus is probably more susceptible than the adult?’” These children could have been exposed to the pesticides in several ways: through farm workers in their families, drift from nearby farms, and home use. However, the most common source of exposure is residue on fruits and vegetables.

To study the effects of OPs on children’s development, CHAMACOS researchers collected urine samples from the moth-ers (before birth), as well as their children throughout the first few years of life, looking for remnants of OP pesticides. Studies in 2007 and 2010 revealed associations between prenatal OP exposure and lower mental development scores and attention skills at two and five years of age, respectively. The seven-year visit helped to determine whether these effects were more long-term, with sig-nificant implications for the children’s future.

Dr. Maryse Bouchard, Dr. Brenda Eskenazi, and colleagues reported the results of the seven-year visit in a recent paper in the journal Environmental Health Perspectives. To assess the mental development of the chil-dren, CHAMACOS employed the Wechsler Intelligence Scale for Children, a test that measures four different areas of intelligence: working memory, processing speed, verbal comprehension, and perceptual reasoning. The test also measures children’s full scale IQ, and does not require reading or writing skills. The researchers asked whether there was a correlation between intelligence and OP exposure. In addition, they attempted to determine whether children were particu-larly vulnerable either before or after birth.

They found that prenatal, but not post-natal, OP exposure had a negative effect on children’s intelligence, particularly when it came to verbal comprehension. Children whose mothers had the highest levels of expo-sure scored, on average, seven points lower in IQ than those whose mothers had the lowest levels. The deficit was apparent even when the researchers controlled for other factors, such as maternal education and exposure to other chemicals. This may not seem like a large difference, but small disadvantages early on in life can often lead to large dispari-ties in development as children grow older.

Alarmingly, these effects may not be confined to rural agricultural communities. While OP exposure levels among women in the Salinas Valley were higher than average for the American population, they were still within the overall range of concentra-tions found in the US. Furthermore, the CHAMACOS study was complemented by those of two Children’s Environmental Health Research Centers in New York City

(at Columbia University and Mount Sinai Medical Center), where OP exposure likely occurred only through home use and food residues. The results suggest that overex-posure to OPs is not limited to agricultural communities, but might be a serious concern in the common American household.

While the use of these pesticides is decreasing in California and nationwide—the EPA reports a 52% decline in use “on foods most frequently consumed by chil-dren” between 1993 and 2004—much of our agricultural production is still heavily dependent on the use of OPs. To deal with these potentially harmful chemicals in our food, Dr. Eskenazi stressed that pregnant women should “eat lots of fruits and veg-etables, because it’s very important for the fetus, for the woman, for her children, but at the same time, make sure to wash those fruits and vegetables well.” She also urged that “keeping chemicals out of one’s life is always a good thing when one is pregnant, and that means everything from using toxic-free makeup and personal care products to fewer plastics, as well as fewer pesticides.”

These results from the CHAMACOS study are only one example of the progress made by the Children’s Environmental Health Research Centers over the past decade —other interesting research investigates how children may not be able to metabolize certain chemicals before a certain age, as well as effects that traffic pollution may have on newborns. While there is still much to learn in the world of public health, research organizations such as CHAMACOS continue to uncover interesting (and potentially alarming) facts about the effects our environment has on our health. New centers have been established to examine environmental contributions to autism, and new initiatives have been directed toward better prevention and diagnosis at both the clinical and public health levels. With any luck, the coming years will yield a greater understanding of the interaction between the environment and children, as well as more effective ways to keep them both healthy.

Molly Sharlach is a graduate student in plant and microbial biology. SE

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One small step for Cal, a quantum leap for mankindAdvances in quantum computingHow does one make a computer faster? Shrink its building blocks and pack in more of them. But there is a fundamental limit to this process: each building block cannot be smaller than a single atom. That limit is not as far-off as it may seem; today’s chip manufacturers are quickly approaching it.

In fact, computer manufacturers rou-tinely construct transistors, computer chip building blocks, with features assembled from only a few thousand atoms. At this scale, physicists have found that matter behaves in ways that are unpredictable from the perspective of standard mechanics. For example, electrons stop behaving like individual particles and start acting more like waves that can interfere and leak from one wire to another. This is one example of what physicists refer to as quantum effects, phenomena governed by the principles of quantum mechanics. Quantum behavior poses a serious challenge for chip manufac-turers, who have been sidestepping certain quantum effects for decades.

Irfan Siddiqi’s Quantum Nano-Electronics Lab (QNL) at UC Berkeley aims to harness the potential benefit of the very quantum effects that plague conventional computers. The lab is hoping to develop the first generation of quantum computers. Recently, the team took a big step toward this goal when they directly observed the quantum behavior of a small system, called a qubit, in real time. Qubits are the potential building blocks of a future generation of powerful quantum computers.

A quantum computer employs the quan-tum behaviors of atoms to speedily perform complex calculations by parallel processing. Whereas each processor in a conventional computer must do computations one-by-one, or serially, quantum effects known as entanglement and superposition would allow a quantum computer to do multiple computations simultaneously, or in parallel. In fact, such a computer could rapidly find the factors of a given large integer by divid-ing it by all smaller integers, all at the same time—a feat that would undermine many modern encryption techniques. In a matter of seconds, a quantum computer could use this advantage to perform a factorization that might take a classical computer the entire age of the universe to compute and use those prime factors to break a code.

How can a quantum computer do more things simultaneously than a classical one? The difference lies in how each system stores information. While a modern laptop stores information in bits, binary pieces of data that are either 1s or 0s, a quantum computer would store information in qubits, short for quantum-bits. These qubits can be 1s or 0s just like bits, but they can also be a combina-tion of the two states. This latter combination is known as a coherent superposition, and it holds the key to a quantum computer’s potentially massive advantage.

A quarter on a table can be thought of as a bit because it can be in one of two states: heads or tails. But what if the quarter is spin-ning on the table? As it spins, it is in neither individual state, but rather something like a superposition of both states. It is potentially both heads and tails, acting like a qubit. If we insist on discovering what state the quarter is in, say by touching it and knocking it down, we collapse this superposition to one of two states: either heads or tails.

Just as a quarter cannot spin forever, a qubit cannot maintain a superposition state forever. It is eventually “knocked down” due to the quantum equivalent of friction. This so-called decoherence scrambles the information stored in the superposition and can introduce insurmountable errors

The inch-long copper box pictured at left holds a tiny quantum circuit on a silicon chip. The chip is connected to the circuit board by aluminum wires thinner than the tip of an eyelash. The qubit, at the top center of the circuit, can “jump” between two quantum states. As shown on the right, an incoming signal interacts with the qubit, and the wave properties are changed depending on the qubit state. The outgoing signal is very weak, about one-millionth the strength of a typical Wi-Fi signal, but the very sensitive JPA amplifier allows it to be measured cleanly.

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in a quantum computation. As Dr. Rajamani Vijay, a postdoctoral researcher at QNL, puts it, “Decoherence is our number one enemy.”

Currently, quantum computers exist only in theory, but the physicists of QNL are hoping to change all that. They began by building their own fundamental building blocks: qubits of their own design. Those made at QNL are essentially “electrical cir-cuits made with similar techniques to [those used to make] computer chips,” according to graduate student Dan Slichter. They are unique in that they are fast, tunable, easy to manipulate, and mass producible with current technology. While the circuits’ speed is important, it comes at the cost of coherence time (how long before the superposition, con-taining the qubit’s information, collapses).

“This is ok,” says Vijay, “so long as each decoherence event can be detected. Then, quantum error correction techniques can compensate for the information loss.” But, as Slichter points out, “individual decoherence event measurements are notoriously difficult, and scientists have been trying to do this for a long time.”

Enter the recent breakthroughs of Siddiqi, Vijay, and Slichter. Their work used qubits made from super-cooled circuits about the size of a human cell, which are too big to display quantum effects at room temperature. At just 0.03 Kelvin—barely above absolute zero—their qubit circuit becomes supercon-ducting, meaning it offers no resistance to currents of electrons trying to flow through it. Inside the qubit, the electrons can behave

in quantum-mechanical unison.When one of these qubits undergoes

a quantum jump from one state to another (like switching from “heads” to “tails”), which may be a signal of a decoherence event, it introduces a tiny shift in the elec-tromagnetic (EM) waves in a nearby sensor. Traditionally, a chain of amplifiers would amplify this signal at the cost of adding noise. This added noise has been so large that it drowns out the quantum jump signal being amplified in the first place.

Here, QNL has made its mark. Using their unique new piece of quantum electron-ics called a Josephson Parametric Amplifier (JPA), the researchers have found a way to maintain the integrity of the quantum jump signal. The JPA mixes the weak jump signal with a “pump tone,” a strong EM wave at the same frequency as the weak signal. This frequency-matched carrier signal amplifies the signal from a single qubit quantum jump above the noise introduced by the later amplification.

By enabling the detection of individual decoherence events in qubits both directly and in real time, QNL cements a key step on the way to the correction of information loss due to decoherence. Their work puts a functional quantum computer, a means of making atom-sized computer building blocks, significantly closer.

Zlatko Minev completed a physics major at UC Berkeley and is now a graduate student at Yale.

At the heart of the qubit are two Josephson junctions (circled in red), formed by placing a thin insulating barrier between two superconducting aluminum wires. The qubit state is determined by whole groups of electrons moving back and forth across the insulating layers of the Josephson junctions. The wires in this scanning electron micrograph image are about 500 atoms wide.

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Rising above Plateau’s problem250 years of mathematical explorationKids love to blow soap bubbles: the bubbles can merge and retain their shape, sparkle, and seemingly defy gravity. Yet these thinly stretched films are more than just fragile physical beauties: they embody on their delicate surfaces truly perplexing structures that have kept mathematicians fascinated for the past three centuries. Jenny Harrison, a Professor of Mathematics at UC Berkeley, has recently worked out the solution to a centuries-old mathematical problem that is best portrayed by soap films and, in doing so, uncovered deep insights to the foundation of mathematical structures.

The question answered by Harrison’s work is known today as “Plateau’s problem”, after Joseph Plateau, a 19th century Belgian physicist who methodically researched the physics of soap bubbles and films. He hypoth-esized that when you dip a loop of metallic wire into a soapy solution, the surface of the soap film formed on the wire represents the minimum mathematically possible area for the loop, no matter what shape the loop is. This theorem is deeply related to a ques-tion first posed in 1760 by the great French mathematician Louis Lagrange: If a simple closed loop is drawn in 3-dimensional space, is there an area-minimizing surface enclosed by the loop?

Area-minimizing surfaces, or simply “minimal surfaces,” are all around you. A flat disc has the smallest area with the boundary of a circle; a sheet of paper has the smallest area with the boundary of a rectangle.

Other minimal surfaces are less common, like the Möbius strip and the catenoid. The catenoid shows that minimal surfaces need not be flat. On the contrary, one mathematical definition of a minimal surface requires that the steepest-uphill and steepest-downhill curvatures be equally steep at every point on the surface, making every point look like a mountain pass or a saddle. Minimal surfaces are even found inside your body: the lipid membranes that enclose your cells are most stable if the hydrophobic middle layer of the sheet is kept isolated from the surrounding water,

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A catenoid is formed when two parallel circular rings are slowly separated after being dipped in a soapy solution, producing a curved minimal surface. Proven to be minimal in 1744 by the great mathematician Leonhard Euler, the catenoid soap bubble adjusts its shape to minimize the area created in three dimen-sional space.

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a configuration that is best achieved by minimizing the membrane’s area.

According to Plateau’s many experi-ments with soap films and bubbles, their structures must not only be minimal but also mathematically smooth (i.e., having derivatives of all orders) and exhibit the lowest possible energy that can be associ-ated with the enclosed surface. Following his discoveries in the late 1800s, the study of soap films garnered much attention in the early 20th century, as many brilliant mathemati-cians strove to find a general mathematical description of their properties. In 1936, Jesse Douglas shared the first Fields Medal (akin to a Nobel Prize of mathematics) for providing a particular class of solutions to Plateau’s problem, but while his special proof was a major step forward, it was not the end of the road. Another 75 years would pass before a fresh look and a novel approach would bring the full, general solution.

In early 2011, Jenny Harrison submit-ted a paper for publication that describes a new approach to Plateau’s problem: one that generalizes all previously studied spe-cial cases, including Douglas’s. Her proof applies to all dimensions and surfaces, from garden-variety surfaces like planes to more exotic ones like Möbius strips, a feat that eluded all previous attempts at a solution and represents a truly astonishing leap in mathematical reasoning.

Harrison began her mathematical exploration of Plateau’s problem in 1986 by trying to find new, simpler, and more general analysis methods for the universal treatment of a wide variety of mathematical surfaces such as fractals, smooth manifolds, and soap

films, as well as physical phenomena like the distribution of electrons on surfaces. In particular, she sought frameworks within which the classical methods of calculus could apply to all of these systems equally. “I spent a good part of the last two decades working in relative isolation on this fascinatingly beautiful problem,” Harrison says. “My goal was to simplify the analytical methods of mathematics and at the same time extend the scope of applications, and isolation was absolutely necessary in order to maintain a state of creative flexibility.”

Harrison’s four-decade-long study of the foundations of geometric proper-ties equipped her with a deepened insight that allowed her to finally take up the formidable challenge of Plateau’s problem when she learned ten years ago that it was still lacking a general solution. (Professor Frederick Almgren of Princeton University had claimed a general solution in 1966 but it was refuted by Professor Frank Morgan of Williams College in 2001) Driven by the problem’s elegance, she spent the last decade converging on the most general framework within which the problem could be solved.

“As I drew closer to the source, I could make out more of what was drawing me in,” she explains. “The problem had evolved into something more beautiful and more power-ful than anything I could ever have hoped to imagine.”

Harrison’s solution, which successfully takes into account all of Joseph Plateau’s foundational experimental observations about soap film surface properties and their unique geometric characteristics, relies fundamentally on a new mathematical framework that she refers to as “Quantum Integration Theory.” Central to this theory are four primitive operators (extrusion, retraction, pre-derivative, and reduction) that act on infinitesimal mathematical objects known as Dirac chains. The operators can be used to move between dimensions, to find relationships between surfaces and their boundaries, and ultimately to prove the existence of a minimal surface enclosed by a boundary—precisely the solution to Plateau’s problem.

The true beauty of Harrison’s solution lies in its generality: because of the efficacy of her Quantum Integration Theory, the

proof spans many applications beyond the easily visualized physical systems of soap films and cellular membranes. Perhaps the most fascinating application introduced in Harrison’s paper is based on a class of novel mathematical operators known as “quantum chain complexes” that could potentially expand our understanding of the mathemati-cal foundations of the physical universe. She was very surprised to find out that the four primitive operators uncovered correspond to the “creation” and “annihilation” operators that are fundamental to quantum field theory, a discovery that could provide new insight to important unsolved questions in quantum physics. “I am not suggesting that we can solve any of these problems, and certainly not without more work,” Harrison cautions,

“but only that the theory provides new tools which may turn out to be very helpful.”

Professor Harrison’s modesty should not diminish the importance of her discov-ery. As the history of scientific discovery demonstrates, creativity can emerge from the intersection of deep explorations and ingenious inventions, a trend embodied by Harrison’s inspiring work. More than just providing a proof of Plateau’s problem, the delineation of her new Quantum Integration Theory could open up entirely unexplored territories in mathematical physics and beyond.

Alireza Moharrer is a solar power engineer in the Bay Area.

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State-of-the-art life science laboratories. Grow your startup one bench at a time.

Work in a dynamic environment, access UC Berkeley core facilities, and enjoy QB3’s renowned support for entrepreneurs.

qb3.org/ebic

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A lab space of one’s own

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A lab space of one’s own

The QB3 Garage: an incubator for innovation

by Susanne Kassube

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California Historical Landmark No. 976 is a mythical place for entrepreneurs. Located at 367 Addison Avenue, Palo

Alto, CA, it is home to the garage in which Bill Hewlett and David Packard developed HP’s first product, the Model 200A audio oscillator. The garage is not only the birth-place of Silicon Valley, but also a symbol for innovation and the Californian entrepre-neurial spirit.

For entrepreneurs in the life sciences, developing ideas into innovative products requires more than what can typically be found in a backyard garage—they need lab space that’s suitable for performing experi-ments in compliance with environmental health and safety regulations. For emerging companies with limited financial means, this space is hard to find in commercial real estate: the minimum unit of lab space that can be rented is around 2,500 square feet, which is too expensive for most beginning entrepreneurs to put on their credit cards.

When Regis Kelly and Douglas Crawford joined the California Institute for Quantitative Biosciences, or QB3, they identified the space issue as one of the main barriers between great scientific discoveries and innovative products that reach the mar-ketplace. They decided to start a tiny incu-bator of ~2,500 square feet at UCSF, which they called the Garage to commemorate HP’s humble place of origin. The smallest unit that can be rented at the Garage is a single lab bench, equivalent to ~120 square feet, which in many cases is sufficient for carrying out proof-of-principle experiments to get the company off the ground. The idea was initially met with skepticism by venture capitalists. “Some of them said don’t bother, this is a recipe for mediocrity, an intensive care unit for small companies that will not amount to anything,” recalls Crawford. “But we proceeded because it was QB3’s strategic goal to promote great science and to help enrich our society. We believe that basic research will lead to economic growth, but

a tiny amount of space, and produce a com-pany of great value,” says Crawford.

From postdoc to entrepreneurThe idea for Fluxion Biosciences was born in Luke Lee’s lab in the Department of Bioengineering at UC Berkeley when Cristian Ionescu-Zanetti, a postdoc at the time, became interested in working outside of aca-demia. He enjoyed his research, but felt that in the academic environment he was, “taking things maybe a fifth of the way towards something that really works, a product that’s better than the status quo.” Together with a graduate student in the lab, he applied for a Small Business Innovation Research (SBIR) grant, entered business-plan competitions, and eventually became the first company to move into the Garage at UCSF. “They came and knocked on our door when we were still planning; we had dedicated the space, but we hadn’t even started to get the approvals from the university,” Crawford says. “In the end, their inquiry for space precipitated it all; it was a nice synergy between us and Fluxion.” While starting the company at the Garage, Ionescu-Zanetti continued working as a postdoc half-time, but soon devoted all his efforts to the company.

Fluxion currently markets two products, called IonFlux and BioFlux. “Technology-wise our focus has always been to take labor-intensive processes, such as drug screening, and parallelize and automate them, to make them faster, better, and cheaper,” explains

if we don’t help it move through the final mile, to get the discovery to the marketplace, we are not meeting our social contract.”

The success story of the QB3 Garage’s first tenant, Fluxion Biosciences, supports Crawford’s point. Founded in 2006, the company moved to South San Francisco in 2008 and now has 30 employees. “When you go there, it’s exactly what people hope for from the science in our universities. Now there’s a small factory in South City, hiring high school graduates to manufacture micro-fluidics devices. It’s the full impact—it’s jobs, it’s cool research tools that will drive future discoveries, and it is the realization of the potential of laboratory research. It showed us that it is possible to start with very little,

“We believe that basic research will lead to

economic growth, but if we don’t help it move through the final mile, to get the discovery to

the marketplace, we are not meeting our

social contract.”

- Douglas CrawfordQB3 Associate Director

Bill Hewlett and David Packard’s garage in Palo Alto, now designated as California Historical Landmark 976.

FEATURES QB3 Garage

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Ionescu-Zanetti. The IonFlux automatically records the flux of ions through membrane channels without the need for intermedi-ate user intervention. The machine uses standard-format multi-well plates commonly used in high-throughput screening, and can be readily adapted to existing screening plat-forms. Pharma companies and academic labs use the IonFlux for screening the effect of drugs on membrane channels, as well as for characterizing the consequences of muta-tions on ion channel currents. Conceptually, the IonFlux was Fluxion’s first product, but after talking to potential customers, the company soon started developing its second product, the Bioflux, which allows research-ers to perform live-cell assays under shear flow. For a variety of applications, such as studies of platelet adhesion that naturally

occurs in the blood stream, the BioFlux mimics the physiological environment much better than traditional assays. The BioFlux instrument is used by scientists in both academia and industry for a number of cell-based assays, ranging from wound-healing research to studies of bacterial microfilms.

“The rewarding moments came after our first instruments went into pharma companies, and their people came back and said, ‘This is much better than what we were doing before.’ They were really excited and even wanted to publish papers with us,” says Ionescu-Zanetti.

Once Fluxion had moved into the Garage, the remaining space filled up quickly. “It’s been full ever since it opened, and we get one to four inquiries a week from nascent companies looking for space,” says Crawford. The increasing demand prompted

Crawford to expand capacity, which led to the creation of the QB3 Garage/Innovation network that now comprises four incubators: the original Garage at UCSF, the Garage at the UC Berkeley campus in Stanley Hall, the QB3 Mission Bay Innovation Center, and finally the QB3 East Bay Innovation Center, which opened in July 2011—and there are already plans for adding the next incubator to the network.

Getting funding in tough timesAllopartis is one of the companies that started out in the QB3 Garage at UCSF and then moved into the Mission Bay Innovation Center, which is now home to more than 20 start-ups. It was cofounded by three former students from Richard Mathies’s lab in the Department of Chemistry at UC Berkeley: Robert Blazej and Nick Toriello, who graduated from the joint UCSF/UC Berkeley Bioengineering graduate program, and Charlie Emrich, a biophysics graduate. One of the hardest things about starting the company was getting funding. “We were founder-financed at the beginning for about 8 months, which meant that all three of us went almost totally broke before we got it funded,” says Emrich. Meeting venture capitalists could sometimes be a surreal experience for someone who had just gotten

QB3 was established in 2000 by Governor Gray Davis as one of four Institutes for Science and Innovation in California and comprises the three UC campuses at Berkeley, San Francisco and Santa Cruz. The aim of QB3 is to accelerate discoveries that will benefit society. Through its Innovation Toolkit, QB3 provides lab space in its incubators as well as mentoring, networking and funding op-portunities for nascent entrepreneurs and connects researchers at its universities with the private sector. QB3 is led by Regis Kelly (left), a neuroscientist and former Vice Chancellor of UCSF. Douglas Crawford (right) joined QB3 as Associate Director after completing his PhD in biochemistry at UCSF.

Fluxion Biosciences founder, Cristian Ionescu-Zanetti, at the UCSF Garage laboratory.

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out of graduate school: “Here we were in our beaten down cars, driving down to Menlo Park where all the venture capitalists work, parking in between a Maserati and a brand new BMW,” says Emrich. Allopartis eventu-ally got funded right around the time when the market crashed, which forced them to be creative with the resources they had. They used the money to prove their core tech-nology, the AlloScreen, and have attracted further investments, including grants from the Department of Energy, ever since.

The AlloScreen employs the principles of directed evolution and a unique selection

system to generate enzymes with optimized properties, such as activity or stability. While natural evolution happens on a timescale of millions of years and relies on spontaneous mutations to create proteins with altered properties, directed evolution in the labora-tory accelerates this process by artificially creating a library of many variants of the original DNA gene that encodes the enzyme. In the AlloScreen, each of the DNA variants is then attached to a substrate particle, and emulsified with the contents of a cell-free expression system in order to produce the many different protein variants that are encoded in each DNA variant. If a particular protein variant is active, it will be able to digest its substrate particle and release its

with Louise Glass in the Department of Plant and Microbial Biology at UC Berkeley, they are now working on co-evolving cellulases with engineered strains of the cellulolytic fungus Neurospora crassa to better under-stand the activity profiles of different types of cellulases.

Crossing the valley of deathAllopartis has successfully crossed what is known among entrepreneurs as the first

“valley of death”—a gap in funding oppor-tunities for projects that go beyond the academic research that the NIH will fund,

but are not yet at a stage of maturity where they can attract commercial funding. Once a start-up has obtained minimal funding to bridge this gap, the next big challenge usually lies in finding affordable equipment. Omniox, a current start-up at the Garage at UCSF, was lucky in that the economic crisis worked in their favor. “Many biotech com-panies were going out of business at the time and sold their equipment, often at bargain prices. We had the deal of a century—we easily got a million worth of equipment for $30,000,” recalls Stephen Cary, co-founder of Omniox.

The company is developing a molecular carrier that will deliver oxygen to hypoxic tissues, areas of the body that are starved

coding DNA, which can subsequently be separated by centrifugation from all the inactive variants, which will stay attached to the bead. The information obtained by sequencing the released DNA molecules is the basis for the further characterization of the altered proteins they encode. Emrich and his colleagues have used the AlloScreen to improve the activity of cellulases, enzymes that digest cellulose. “Cellulose is the most abundant biopolymer on earth,” explains Emrich, “it is a linear chain of glucose molecules, and these chains are magically very crystalline, not very soluble, and very

recalcitrant, so they do not break down easily.” Because of these properties, cellulosic enzymes are the holy grail in the making of biofuels. While glucose can relatively easily be fermented into ethanol, breaking down cellulose into glucose is the rate-limiting step. With improved cellulases, abundant and renewable resources such as agricultural waste and non-food crops could be used for the production of low-emission biofuels that could substitute fossil fuels and lower green-house gas emissions. Although getting there will be a long journey, scientists at Allopartis have already created cellulase variants with improved activity and are optimistic. “We’re now getting some commercial traction for those variants,” says Emrich. In collaboration

“We had the deal of a century—we easily got a million dollars worth of equipment for $30,000.”

- Stephen Cary, co-founder of Omniox

FEATURES QB3 Garage

Robert Blazej, co-founder of Allopartis, working in his lab-oratory at the UCSF Garage.

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of oxygen such as tumors. The first pro-tein that comes to mind for this purpose is hemoglobin, the protein that transports oxygen from the lungs to all other tissues in the body. However, government agencies and companies have tried for decades to develop hemoglobin into an oxygen transporter that could be used as a blood substitute, with no success: taken out of red blood cells, hemoglobin scavenges nitric oxide, with devastating effects for the body.

It was during his final days as a gradu-ate student in Michael Marletta’s lab in the Department of Molecular and Cell Biology at UC Berkeley when Cary had an idea that seemed too good to be true: “I was read-ing up on all the efforts around developing

hemoglobin as an oxygen delivery therapeu-tic, reading paper after paper about how the FDA was rejecting it for trauma and surgery because of the toxicities, when I suddenly remembered a group meeting from a few weeks before where Elizabeth Boon, a post-doc in the lab, had presented on a protein that didn’t have very much nitric oxide reactivity, and I thought wait a minute, maybe this is a much better platform, because it’s a stable gas sensor, rather than being a gas reactor.” The protein is part of the heme nitric oxide/oxygen binding family, or H-NOX. Like hemoglobin, it uses heme as a cofactor, but subtle differences in the coordination geometry result in very different oxygen-binding properties. Cary presented his idea

to Jonathan Winger, a postdoc in the lab, and together with Marletta they success-fully applied for a Rogers Bridging-the-Gap Award for translational research at QB3. To develop their idea further, they founded Omniox and Emily Weinert, a postdoc in the Marletta lab, created and characterized more variants of the protein with a range of oxygen binding affinities. Under Cary’s leadership and supported by a National Cancer Institute SBIR grant, the company then moved into the Garage at UCSF.

The H-NOX protein could potentially be used as a therapeutic in many different diseases that are associated with hypoxia. Potential applications include treating stroke, managing sickle cell pain, and wound

Business plan competitions are a great opportunity for budding entrepreneurs to raise funding, network, and get in touch with venture capitalists. The UC Berkeley Business Plan Competition (BPlan) is organized by MBA students and held annually at the Haas School of Business.

The Rogers Bridging-the-Gap Award enables teams of re-searchers led by a QB3 faculty member to develop ideas with the potential to benefit society. Desired outcomes are filing of intellectual property patents and incorporation of a company. The award is administered by QB3 and supported by the Rog-ers Family Foundation. Three projects are funded with up to $100,000 each per year over a two-year period.

Small business innovation research (SBIR) grants are federal research funds that support projects that have the potential for commercialization. A Phase I grant is worth $150,000

and allows nascent companies to conduct proof-of-principle experiments to establish feasibility of their concept. Success-ful Phase I awardees can apply for a $1 million Phase II grant to develop their projects further. Crawford recommends filing an SBIR grant early, while still at the university as a postdoc or graduate student: “It’s a very productive way of starting a company. It forces you to focus on what your most important milestone is, and if the grant is funded, you don’t have to go through the extreme poverty in the beginning stage of the company.”

Mission Bay Capital (MBC) is a seed-stage venture fund managed by QB3’s Regis Kelly and Douglas Crawford on a pro bono basis and supported by venture capitalist experts Brook Byers and John Wadsworth. MBC funds four companies per year with ~$500,000 each.

Initial idea, incorporate company.

($1200)

QB3 support (Space,

Mentoring) Obtain

equipment and develop technology.

Rogers Bridging-the-Gap Award,

SBIR Grants

First “Valley of

Death”

Further develop technology /

Pre-clinical studies.($1 - 3 Million)

Phase III SBIR funding and

additional venture capital

Second “Valley of

Death”

Commercialization / Clinical studies

($15 - 100 Million)

Pathway of success for QB3 Garage start-ups

FEATURES QB3 Garage

Funding opportunities

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been able to make spider silk recombinantly on a commercial scale,” explains David Breslauer, a graduate from the joint UCSF/UC Berkeley Bioengineering graduate pro-gram. Together with two other graduates from the same program, Dan Widmaier and Ethan Mirsky, Breslauer co-founded Refactored Materials and has been a tenant at the Garage at UCSF since May 2010. They decided to use yeast cells for the recombinant production of the large silk proteins, and have already produced enough silk protein to try to make fibers. “Fibers are generally either melt-spun, meaning that you melt a polymer, extrude, and cool it, or wet-spun, meaning that you dissolve a polymer and extrude it into a non-solvent that coagulates it,” explains Breslauer.

In contrast to many other emerging companies, Refactored Materials was funded from the beginning: they got their first grant right when Breslauer graduated. Although the company is now minimally funded through federal and state grants for several years, they’re still looking for additional sources of money: “We’re moving faster than those grants can support,” explains Breslauer.

“It’s nice to have them, but it’s not necessarily something to rely on.”

While the first six months at the Garage felt very similar to working in an academic environment for Breslauer, the mindset changed once they started to work harder

three years. The company will then face what Crawford calls “the second valley of death.” QB3 has worked hard toward bridging the first valley of death by providing mentor-ing, funding, and lab space to start-ups, but bridging the second valley of death, the gap between pre-clinical and clinical studies, poses further difficulties: “The enterprise back at the discovery end is expensive, but the cost in the clinic dwarfs that,” explains Crawford. Cary estimates the costs for phase I and II studies at around $15 million; get-ting H-NOX to the market through phase III studies will add another $50 to $100 million. But, given Omniox’s latest results, it seems likely that they will find investors willing to pitch in to help get Omniox to work in helping cancer patients.

From bench to businessOne of Omniox’s neighbors at the Garage at UCSF is Refactored Materials, a start-up that works towards the synthetic produc-tion of spider silk. Spider silk is a material of phenomenal strength, lightness, and flexibility that outperforms all man-made materials and could potentially be used in applications ranging from lightweight and durable clothing to artificial tendons. A big challenge for commercialization is the production of spider silk: “Spiders can’t be farmed, they’re territorial, they will attack each other, eat each other, and no one has

Refactored Materials co-founders, Dan Widmaier (left) and David Breslauer (right), examine spider silk fibers at the UCSF Garage.

healing. Although Cary considers branch-ing out, the company currently focuses on overcoming hypoxia in tumors. “Hypoxia is a huge driver of tumorigenesis and metastasis,” explains Cary. If the growth of blood vessels can’t keep up with the growth of the tumor, large regions are starved of oxygen. Those regions are hard to target using conventional therapies such as radiation, which relies on the damaging effects of reactive oxygen spe-cies. In addition, cells in the hypoxic regions usually become more aggressive as a conse-quence of being starved of nutrients, energy, and oxygen, and tend to form metastases in other parts of the body. The goal of Omniox is to improve existing cancer therapies by bringing oxygen to the tumor. Initial studies using a mouse model show that the protein very efficiently travels from blood vessels into the tumor tissue to deliver oxygen to previously hypoxic areas—a phenomenal success that was rewarded with a $3 mil-lion SBIR Phase II Award from the National Cancer Institute. Omniox is now eligible to apply for a SBIR Bridge Award if they can secure matching funds from private inves-tors, which would add another $6 million to their budget. These funds will pay the costs of optimizing a lead candidate that will then be used for pre-clinical studies to determine its efficacy and its toxicity profile in animals. If all goes well, H-NOX will be ready for clinical studies in about two to

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on developing the business aspect. “You sud-denly stop caring as much about publications, you’re just trying to make something that really works, rather than understand every little detail about it,” Breslauer remembers.

Strategic partners to finance growthSilicon BioDevices was the second company to move into the Garage at Berkeley after it opened its doors in summer 2010. The company is developing diagnostic devices that are based on digital microchips and can detect tiny amounts of specific proteins in a liquid sample such as blood. The ease of use combined with high sensitivity and low costs—the single-use device will be available for $1.50—sets them apart from the bulky and expensive analyzers that are currently available on the diagnostics market.

Once a drop of whole blood is applied, a membrane at the top of the device separates red blood cells from the plasma. The plasma then solubilizes antibody-coated magnetic particles on the back of the membrane, allow-ing them to bind the protein to be detected and a secondary antibody. Nonspecifically bound particles are removed magnetically, and the remaining particles are detected by the chip. After the signal is read out and processed, the test result can be sent directly to the physician’s cell phone by a wireless transceiver that is integrated into the device. A significant advantage with regard

to safety is the self-testing capability of the device: “The sensor can control the assay by making sure it’s run correctly, in a timely way, and you can disable it if it has been compromised in any way,” explains Silicon BioDevices’ co-founder Octavian Florescu, a graduate from Bernhard Boser’s lab in the Department of Electrical Engineering and Computer Science at UC Berkeley.

The user-friendly design might eventu-ally allow for diagnostics at home, but for the near future Florescu hopes that the device will find its way into emergency departments and physician’s offices, rendering time-consuming laboratory testing obsolete. “The number one reason doctors don’t perform in-office testing is because it requires extra time and extra staff,” says Florescu. The device would be the first highly sensitive diagnostic tool that could be integrated seamlessly into a physician’s workflow.

Although initial results are promising, it might still be another three years until you encounter one of Florescu’s chips at your local doctor’s office. Developing the final prototype and making it manufacturable will take approximately two years before the device is ready for approval by the FDA, which might then take another year.

The company has raised money from

business plan competitions, but is financed out of Florescu’s pocket for the main part. In order to finance further development and production, the company is now approaching life science investors and strategic partners.

“It’s a very slow process; even if you have a great technology, you have to add another 12 to 18 months to strike a good deal,” explains Florescu.

Judging from the history of its prede-cessors at the Garage, it seems likely that Silicon BioDevices will be able to close a deal: out of the first six companies that started at the Garage at UCSF, four closed venture financing rounds and a fifth was acquired by Affymetrix for $25 million. “There’s now one very wealthy 28 or 29-year old after start-ing a biotech company at the Garage,” says Crawford, adding: “We’re not promising that for everyone, but it’s nice to know that there is at least that possibility.”

Starting a start-upContrary to what one might think, the high success rate is not based on an evaluation of the commercial potential of the companies by QB3. “We don’t want to be rigorous in the evaluation of the market opportunity of what they brought to us, we want to be rigorous in our evaluation of the people. Most real innovations are diamonds in the rough: over and over again, we don’t see it when it comes. If you have good people, you get to the right conclusions most of the time, and we want to help them grow as quickly as possible,” says Crawford.

Cary’s advice for nascent entrepreneurs? Just do it! “You can be a postdoc with an idea, and you can start a company. For $1,200 you incorporate your company, then you take your science idea and submit it as a six-page SBIR grant, and eventually you get half a mil-lion dollars.” Although the process might not always be so smooth, starting a company is a rewarding experience, says Crawford: “I do not know of a single case where an individual regretted their decision. All admit that it’s the hardest thing they’ve ever done, stressful, but satisfying in a way that then exceeds their expectations.” So, what are you waiting for?

Susanne Kassube is a graduate student in biophysics.

“You suddenly stop caring as much

about publications, you’re just trying to

make something that really works.”

David BreslauerRefactored co-founder

Spools of Refactored recombinant spider silk.

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The science behind positive psychology

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s the story goes, University of Pennsylvania psycholo-gist Martin Seligman, a self-described pessimist, was weeding his garden

when his five-year-old daughter Nikki began playfully shrieking and tossing weeds in the air. As Seligman scolded her harshly for being disruptive, his daughter spun around, looked Seligman in the eye, and said: “Daddy, stop being such a grouch!”

Seligman says that he took this as a wake-up call. Being a pessimist was some-thing he could deal with, even something to be proud of in his academic circles, yet being called a grouch made him cringe. His research up to this point centered on the roots of depression, but the gardening incident made Seligman realize that he, and perhaps the field of psychology as a whole, had focused solely on negativity for too long. So, shortly after his appointment as president of the American Psychological Association in 1998, Seligman charted out a new approach for the field. Dubbed “positive psychology,” this branch of research would focus on human thriving over human pathology—studying function over dysfunction.

The movement quickly developed a fol-lowing, including at UC Berkeley. At around the same time, an entirely separate journey brought two Cal alumni, Tom and Ruth Hornaday, back to their alma mater. The Hornadays had recently dealt with a tragic family loss, and came to Berkeley in 2001 with the idea of funding multidisciplinary research on social and emotional well-being. After speaking with several Berkeley

by Azeen Ghorayshi

The brain ishalf full

professors already studying the positive psychology topics that they wanted to help promote, the Hornadays created the Greater Good Science Center (GGSC).

Housed within the UC Berkeley Child Study Center on the south side of campus, the GGSC offers undergraduate and gradu-ate research fellowships, holds community lectures, and publishes the online Greater Good magazine to highlight current research in the field. With the belief that positive human traits are innate and strongly tied to individual thriving, the GGSC and its positive psychology peers hope to promote the elusive holy grail of personal achieve-ment—true happiness.

Our better halvesBefore the field of positive psychology could really get off the ground, it needed a mani-festo of sorts—a clearly paved vision for its new focus on positive human behaviors. To create the common language and standard-ized protocols necessary for a rigorous sci-entific discipline, Seligman and his cohorts wrote the Character Strengths and Virtues (CSV) manual—equivalent in purpose, but opposite in focus, to the Diagnostic and Statistic Manual of Mental Disorders (DSM) used to characterize psychological condi-tions for over 50 years. Psychology up to that point, said Seligman, had studied “only half of the landscape of the human condition,” and the CSV would thus serve as the DSM’s natural counterpart.

The manual lays out the central tenets of the positive psychology field. The main idea is that virtues such as compassion, courage,

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and wisdom are as much a part of our human nature as selfishness, weakness, or ignorance. Therefore, just as psychological illnesses need to be identified, treated, and prevented, an academic study of human strengths is needed to help understand and therefore better cultivate good character. Perhaps most importantly, Seligman explains that tuning in to our collective positive natures will not only make us better people, it can also make us happier.

In keeping with the tenets of positive psychologists, the professors at Berkeley’s Greater Good Science Center strongly sup-port the idea that humans are hard-wired to care, and in turn that caring creates happier individuals. One of their primary research focuses has therefore been on altruism, the sometimes puzzling phenomenon where people put the well-being of others—occa-sionally even strangers—before their own.

The question of whether or not truly “altruistic” altruism exists has divided social psychologists for years. On one side of this so-called “altruism question” is the idea that cooperation and kindness mask deeper, sometimes unconscious, self-interest. On the side of the GGSC and the positive psychologists is the belief that there is a truly evolved altruism woven into our emotional makeup. “One of the biggest challenges to the claim of sincere altruism is that what you’re seeing is really a strategic pursuit of prestige or reputational gain,” says sociology professor and GGSC affiliate Robb Willer.

“Well, we wanted to show that not everyone

is driven by that.” To do this, Willer and GGSC co-founder

Dacher Keltner teamed up at Keltner’s Social Interaction Laboratory to separate genuine altruism from its less virtuous counterparts based on a variety of measures. First, they separated the public and the private spheres of social interaction; in a measure of genu-ine altruism, individuals concerned with public opinion would presumably be more selfish when given the opportunity to act anonymously.

As a test of this model, a group of 94 undergraduate research participants were first given a written evaluation to determine their self-perceived generosity. They then acted as the subjects in a series of economic scenarios designed to test how likely they were to allocate a pool of resources—to be exchanged at the end of the experiment for real money—to another individual. In the

“private” condition, there was no third party viewing the transactions, and the subject was only identified by a letter. In the “public” condition, a third party was present to see how much, if any, of the resources the subject decided to share. But here was the catch: the third party could potentially return money to them as well, giving the subjects a repu-tational incentive to act more “prosocially” than they otherwise might.

What Keltner and Willer saw emerge was a “sincerely altruistic” group that sustained stably high levels of generosity regardless of the public or private conditions. In contrast, more “reputationally altruistic” people acted

prosocially in the public condition, but their generosity dropped off significantly when given the opportunity to act unwatched. Further testing showed that the sincerely altruistic group both placed less personal value on status and sustained their levels of generosity after going through a classic experimental construct designed to disable their ability to pretend. “A lot of people

In 1872, Charles Darwin published The Expression of the Emotions in Man and Animals, a hereditary study of behavior. At the time, the dominant belief was that humans possessed unique and divinely created muscles to express emotions. In Expression, however, Darwin claims that our emotional capabilities are subject to natural selection. Using detailed illustrations and close analyses of physiological responses to different emotions—such as hair raising, vocal emissions, perspiration, and the precise movement of facial muscles—Darwin traces purposeful links between expressions of emotion in animals to their human equivalents. He concludes, “the young and the old of widely different races, both with man and animals, express the same state of mind by the same movements.” Notably, the book was also the first scientific text to make use of the new medium of photography.

After observing domesticated family pets and wild animals like swans, chimpanzees, and wolves, Darwin carefully recorded animal responses such as purring, snarling, and tail-wagging.

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FEATURES Positive psychology

think that we are not generally ‘good’ as a species—that we are bloody, violent and genocidal,” says Keltner. “These negative aspects have a clear evolutionary story, but we want to show that our prosocial side as a species is equally important in really think-ing about who we are and how to cultivate mental health.”

This idea is key to both the positive

psychologists’ and the GGSC’s approach; they do not disregard the weaknesses inher-ent in human nature. Rather, they argue that by working to better understand what can make us good, we could work to make ourselves better.

Alongside their goal of studying what makes an individual inherently “good” is the concept that virtue and happiness are heavily intertwined—a concept called eudae-monia that dates back to the ancient Greeks. Showing that there is such a thing as truly innate altruism is thus crucial to their idea that tapping in to our shared inner generosity can increase our personal well-being. Help others, they say, and you can help yourself.

An empathetic geneKeltner is something of a celebrity in the popular psychology world. He has shoulder-length silvery blonde hair and exudes the sort of calm eloquence one might expect from a surfer-turned-academic. His research is regularly featured in major media outlets like The New York Times, Nightline, CNN, and Oprah. And so it is no surprise that his undergraduate psychology course, “Human Happiness,” is one of the most popular classes at Berkeley.

In the class, Keltner often asks his stu-dents the following question: Where do our individual senses of morality come from?

“They will usually give me one of several true, but only partially true, answers—from their parents, from their culture, from their religion, from the books that they read,”

says Keltner. “But in the last fifteen years psychologists have really started to think about how morality is also rooted in evolu-tion and genetics.” Raising the more specific question: Where is something like morality located inside of us?

In 1872, thirteen years after the publi-cation of On the Origin of Species, Charles Darwin attempted to find the evolutionary roots of what was until then thought to be a distinctly human characteristic—emotion. In The Expression of the Emotions in Man and Animals, Darwin took a plethora of human feelings—such as anger, grief, shame, sympathy, and joy—and attempted to find their animal equivalents.

“Until that point, Western culture believed that our incredibly complex emo-tional capacity was associated with a feel-ing of the sacred, and therefore had to be God-given,” says Keltner. “What Darwin said is that these emotions are really as much a part of our evolutionary heritage as the other traits he had studied.”

Working with the idea that our emo-tional capabilities are coded somewhere within our genomes, Keltner teamed up with Sarina Rodrigues, a post-doctoral candidate in the GGSC’s research fellowship program. Rodrigues was interested in a hormone and neuromodulator called oxytocin—some-times referred to as “the love hormone.”

Oxytocin exploded in popularity in the early 1990s for its well-established roles in emotional behaviors like parenting and pair-bond formation. In animals such as the

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female prairie vole, for example, oxytocin released during physical contact with a male has been strongly implicated in establishing the vole’s lifelong monogamy. In humans, the hormone was initially only known to have effects on pregnancy and labor, but in the past ten years increasing evidence has pointed to its involvement in complex emotional brain processes such as trust, generosity, and even love.

Oxytocin can act both as a hormone, traveling long distances through the blood-stream to carry out effects far from its origin in the brain, and as a neurotransmitter, binding to small proteins called receptors on the surface of neurons to cause changes in firing. Since Keltner and Rodrigues were interested in empathy, they focused their project on oxytocin’s effect at the neuronal level, looking at the two known versions of the oxytocin receptor (see “Can you second my emotion?” BSR Fall 2010). Located on the third chromosome of the human genome, the two variants differ by only a single nucleotide—a guanine (G) in one version

is switched to an adenine (A) in the other. Although the difference seems trivial, it had previously been implicated in some interest-ing behavioral differences, so they decided to take a closer look. After genotyping a group of 192 participants to determine which of the two variants each person expressed, Rodrigues put the subjects through a battery of behavioral tests and self-reports to identify their potential differences in empathy.

Rodrigues and Keltner relied on the well-established fact that empathy is closely tied to an understanding of other people’s emotions—a capability often lacking in individuals with genetic disorders such as autism. Using a standardized empathy measure called “Reading the Mind in the Eyes,” participants were shown 36 black-and-white pictures of people’s eyes and then asked to choose the word that best described the subject’s apparent mood. They also tested all of the participants for their relative stress reactivity, in keeping with oxytocin’s known calming effects.

What they found was that subjects with the G variant consistently scored higher on the eye-reading task and lower on the stress test than subjects with the A variant. Although the differences were not always hugely significant, the results indicated that a single nucleotide difference in the genetic code could potentially be tied to something as complex as empathy. “I came into this research as a big skeptic,” said Rodrigues in a New York Times article about oxytocin published shortly after her paper came out,

“but the results had me floored.”Her findings, published in 2009, were

added to the slew of recent papers regarding oxytocin’s role in many of the emotional processes that we most associate with being human. And yet, according to both Keltner and Rodrigues, the oxytocin study does not suggest that there are inherently empathetic or unempathetic people; a genetic correlate rarely indicates fixed, unchanging character-istics. Rather, they say, it’s just one element, and perhaps a strong jumping-off point, for something much more complex. For example, take a child’s height. “This is a trait that is 100% heritable, and it’s still very susceptible to environmental intervention—if you feed kids better, they grow taller,” says Philip Cowan, an executive faculty member of the

GGSC who studies applied developmental psychology. “So you can’t even think about genetics without environmental context, and you certainly can’t think about envi-ronmental context without genetics.” Their goal is that with an increased understanding of how positive behaviors are rooted in our genes, we can work to better cultivate them environmentally.

A nurturing nature“We know there are empathetic and prosocial children, and as a scientist you want to figure out the physiological underpinnings of that profile,” says Keltner. “But also, and this is where the GGSC comes in a lot, how do you make kids more empathetic?” Much of this branch of research has to do with “positive interventions”—positive psychology’s pre-ventative, prosocial counterpart to classical psychology’s interventions implemented when antisocial behaviors reach a breaking point.

Cowan, who has worked for 40 years with his wife Carolyn on family systems and child development, focuses primarily on positive interventions in the earliest stages of life—the prenatal and early childhood periods. In a longitudinal study published in 2011, the Cowans showed that of 100 two-parent couples raising their first child, those who attended regular couples’ therapy before their child’s first year of kindergar-ten were able to sustain a much more stable family system for ten years after the sessions were complete. Furthermore, the children of parents who underwent therapy showed increased academic and social competence compared to the no-therapy controls.

“The goal is to get in very early and focus on the systems of family relationship, not just an ideal of ‘good parenting.’ You have to look at all of the relationships in the system,” says Cowan.

And this is where the real impact of the GGSC lies—highlighting the ways in which new research can concretely improve people’s lives. Though Cowan looks at the applica-tion of principles out in the field, a lot of potentially applicable psychology research never makes it too far out of the lab. When the Hornadays established the GGSC, they were looking to establish a pipeline from the social science labs directly to the people it

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FEATURES Positive psychology

could benefit. This pipeline has largely come in the form of the GGSC’s popular online magazine, Greater Good.

“There was a growing body of evidence supporting a different way of viewing our human nature,” says Jason Marsh, Editor in Chief of the magazine. “We saw that there was a great need for a publication with the mission of featuring this research and put-ting it into terms that are more accessible to the general public.”

The magazine provides in-depth articles, guest columns from researchers, and even a popular parenting blog called “Raising Happiness.” From slightly more tongue-in-cheek quizzes such as “Is she flirting with you?” (an emotional intelligence quiz), to a Father’s Day article explaining how to get dads more involved in child-rearing (written by Cowan and his wife), the magazine’s con-tent ranges from light and playful to serious and contemplative. It also advertises their community seminar series, started in 2009, where people in the science, education, and public policy communities speak on topics ranging from increasing altruism in kids to sustaining thriving romantic relationships.

“The study of human behavior is what we’re all always talking about anyway—it’s what people talk about in bars, what people gossip about in barbershops,” says Willer.

“But Greater Good’s focus on the cutting-edge research about this stuff is what makes it much more rigorous than your typical sci-entific public outreach project.”

The market of happinessBut what about Martin Seligman’s new campaign for positivity? Shortly after his official launch of positive psychology in 1998, something strange started happening—the American public got hooked. In 2000, less than 250 books were published on happiness, most in the way of self-help manuals. In 2010, over 2,300 books were published on the topic.

Browse the self-help aisle of your near-est bookstore and you will inevitably find the following titles: Happiness: The Science Behind Your Smile, What Happy People Know: How the New Science of Happiness Can Change Your Life for the Better, and The Happiness Project: Or, Why I Spent a Year Trying to Sing in the Morning, Clean My Closets, Fight Right, Read Aristotle, and

Generally Have More Fun. Now, with websites and smartphone applications devoted to a continuously more personalized view of user experience, people can even track their own happiness in real-time and correlate it with where they are located and what they are doing. We want to know exactly what this happiness thing is and how to get more of it.

So it happened that the positive psychol-ogy movement came with its own particular form of backlash—a popular marketplace promising “scientific” understanding of hap-piness in exchange for money, money, and more money. Seligman, as the figurehead of the field that spawned a cultural move-ment, received a fair amount of criticism. In 2004, he published his own bestseller, Authentic Happiness: Using the New Positive Psychology to Realize Your Potential for Lasting Fulfillment. But, many critics argued, how could such a young field of scientific research already have the answer to such an age-old, elusive question?

The problem, critics said, stemmed from two things: first, happiness is difficult to objectively measure, and second, by focus-ing so heavily on “happiness,” Seligman was missing the point of a more broadly fulfilling life, and perhaps selling out to the lucrative popular market-place of happiness.

The core of the mea-surement issue is that if happiness is necessarily subjective, then self-reports are unavoidable.

“In psychology, we like to be able to use more concrete measures than just self-reports,” says Willer. “Ideally, we would like to have behavioral or physiological signatures for happiness, but that is very difficult to do—and that is a challenge for the field. That said, I think these are healthy criticisms that positive psychologists are really working hard to listen and respond to.”

On the point of the over-pursuit of happiness,

however, Seligman himself seems to have backtracked slightly in recent years. His new book, Flourish, even lengthily derides the so-called “happiology” that many critics would argue he helped to create, saying that he never meant for positive psychology to be construed as a prescription for a pleasant life.

“Happiness is a diffuse term,” says Keltner. “By solely asking, ‘Am I happy?’ we miss out on the many nuances of a meaningful life.”

Nevertheless, positive psychology as a field is thriving. Classes like Keltner’s are now taught on over 200 college campuses nationwide, and a steadily increasing number of psychologists are turning to “positive” research topics. Regardless of whether the secret to a happy life will ever be definitively understood, institutions like the GGSC see their roles as solid—connecting people to the research that defines their lives. “Happiness is very important,” says Marsh. “But it’s only one part of the puzzle. We’ve got a lot to figure out along the way.”

Azeen Ghorayshi is a lab technician in molecular and cell biology.

Page 36: Berkeley Science Review - Fall 2011

34 Berkeley Science Review Fall 2011

your click.

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your pick.

Vote online to make sure your favorite article wins.

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Fall 2011 45Berkeley Science Review

atural history collections around the world contain over one billion specimens, and

could reveal important changes in biologi-cal systems that have occurred over the past 100–200 years. In the internet age, you might expect that specimen data would exist in online databases, but this is not the case for most museums. The painstaking endeavor to make natural history collections digitally accessible requires huge data entry efforts and the coordination of interdisciplinary teams of scientists.

Biologists of diverse disciplines are increasingly collaborating with computer programmers to create efficient data man-agement and dissemination systems. John Wieczorek is a programmer whose domestic partner, Dr. Eileen Lacey, happens to be cura-tor of mammals in the Museum of Vertebrate Zoology (MVZ) at Berkeley. One day in 1997 Eileen came home from work and said to John, “Hey, they have this picture of a database on the wall in the museum, and I don’t think anybody there understands it. Why don’t you go in and see if you can help them out?” John was initially doubtful, until she came home two weeks later to say the same thing. He recalls thinking, “Well, she’s going to do this until I go look at that damn database picture on the wall,” so he agreed to go in for a meeting a few days later. To his surprise, that meeting turned out to be an interview where he accepted a position to develop a modern relational database that would handle all of the collection data in the museum. He has proceeded to become a leader in the global effort to make informa-tion from natural history museums acces-sible to anyone with an internet connection.

Wieczorek is but one important player in the ongoing, interdisciplinary efforts neces-sary to get collections data online and in a central location. The standardization and centralization of specimen databases—docu-menting everything from large mammals to tiny insects and plants—is essential for understanding historical biodiversity and how it has changed over the past century

Movingnatural history

collections online

by Joan Ball

MA

REK

JAKU

BOW

SKI

NDigitizing the Drawers

Digitizing the Drawers

36 Berkeley Science Review Fall 2011 Fall 2011 37Berkeley Science Review

There’s a

MAPfor that

Cell phones for a better commute

by Ginger Jui

ERIC

FIS

CHER

ooking down and across the San Francisco Bay from the Berkeley hills during the evening rush hour, one sees an umbilicus of traffic—amber headlights on the left, ruby taillights on the right—stretching across the Bay Bridge, con-

necting the gridded East Bay streets to the skyline of San Francisco. A traffic engineer admiring this scene might ask: “Where are all these people going?” “Is traffic this bad everyday?” or “How can we make it f low faster and more efficiently?” Increasingly, the need for real-world solutions to traffic problems requires transcribing this bird’s-eye view of traffic information into actual hard data on a computer. This task requires ubiquitous technology allowing individuals to transmit information about their environ-ment, as well as the computational power to amass and analyze this data at break-neck speeds. Today, UC Berkeley researchers are merging the fields of civil engineering and information technology to bridge these information gaps between the traffic models on their computers and the drivers on the ground.

Real-time traffic information is a valuable commodity. For over 40 years, the major source of traffic information for the California Department of Transportation (Caltrans) has been loop detectors. These are the thick cables embedded as a circle or hexagon in the asphalt of highway lanes that are also commonly used to detect whether cars are stopped at stoplights. Historically, Caltrans invested in loop detectors because they report the three main pieces of infor-mation—traffic speed, volume, and occu-pancy—necessary for generating a complete picture of highway conditions. However, loop detectors are expensive to build, highly sensitive, and difficult to maintain, requiring Caltrans to shut down whole lanes of traffic if an array of detectors goes haywire. As California state budgets continue to shrink, Caltrans is looking for cheaper and more effective alternatives for gathering traffic information.

One such alternative is now available in the form of Global Positioning System (GPS) data from mobile devices. GPS data

L

20 Berkeley Science Review Fall 2011 Fall 2011 21Berkeley Science Review

A lab space of one’s own

The QB3 Garage: an incubator for innovation

by Susanne Kassube

EGG

NES

T: F

RIZZ

YCH

ICK;

DES

IGN

: VA

LERI

E O

’SH

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Fall 2011 29Berkeley Science Review

LEA

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ND

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s the story goes, University of Pennsylvania psycholo-gist Martin Seligman, a self-described pessimist, was weeding his garden

when his five-year-old daughter Nikki began playfully shrieking and tossing weeds in the air. As Seligman scolded her harshly for being disruptive, his daughter spun around, looked Seligman in the eye, and said: “Daddy, stop being such a grouch!”

Seligman says that he took this as a wake-up call. Being a pessimist was some-thing he could deal with, even something to be proud of in his academic circles, yet being called a grouch made him cringe. His research up to this point centered on the roots of depression, but the gardening incident made Seligman realize that he, and perhaps the field of psychology as a whole, had focused solely on negativity for too long. So, shortly after his appointment as president of the American Psychological Association in 1998, Seligman charted out a new approach for the field. Dubbed “positive psychology,” this branch of research would focus on human thriving over human pathology—studying function over dysfunction.

The movement quickly developed a fol-lowing, including at UC Berkeley. At around the same time, an entirely separate journey brought two Cal alumni, Tom and Ruth Hornaday, back to their alma mater. The Hornadays had recently dealt with a tragic family loss, and came to Berkeley in 2001 with the idea of funding multidisciplinary research on social and emotional well-being. After speaking with several Berkeley profes-sors already studying the positive psychology topics that they wanted to help promote, the

by Azeen Ghorayshi

The science behind positive psychology

The brain ishalf full

Hornadays created the Greater Good Science Center (GGSC).

Housed within the UC Berkeley Child Study Center on the south side of campus, the GGSC offers undergraduate and gradu-ate research fellowships, holds community lectures, and publishes the online Greater Good magazine to highlight current research in the field. With the belief that positive human traits are innate and strongly tied to individual thriving, the GGSC and its positive psychology peers hope to promote the elusive holy grail of personal achieve-ment—true happiness.

Our better halvesBefore the field of positive psychology could really get off the ground, it needed a mani-festo of sorts—a clearly paved vision for its new focus on positive human behaviors. To create the common language and standard-ized protocols necessary for a rigorous sci-entific discipline, Seligman and his cohorts wrote the Character Strengths and Virtues (CSV) manual—equivalent in purpose, but opposite in focus, to the Diagnostic and Statistic Manual of Mental Disorders (DSM) used to characterize psychological condi-tions for over 50 years. Psychology up to that point, said Seligman, had studied “only half of the landscape of the human condition,” and the CSV would thus serve as the DSM’s natural counterpart.

The manual lays out the central tenets of the positive psychology field. The main idea is that virtues such as compassion, courage, and wisdom are as much a part of our human nature as selfishness, weakness, or ignorance. Therefore, just as psychological illnesses need to be identified, treated, and prevented,

sciencereview.berkeley.edu

Page 37: Berkeley Science Review - Fall 2011

Fall 2011 35Berkeley Science Review

your click.

sciencereview.berkeley.edu/award

your pick.

Vote online to make sure your favorite article wins.

Reader’s Choice Award

Fall 2011 45Berkeley Science Review

atural history collections around the world contain over one billion specimens, and

could reveal important changes in biologi-cal systems that have occurred over the past 100–200 years. In the internet age, you might expect that specimen data would exist in online databases, but this is not the case for most museums. The painstaking endeavor to make natural history collections digitally accessible requires huge data entry efforts and the coordination of interdisciplinary teams of scientists.

Biologists of diverse disciplines are increasingly collaborating with computer programmers to create efficient data man-agement and dissemination systems. John Wieczorek is a programmer whose domestic partner, Dr. Eileen Lacey, happens to be cura-tor of mammals in the Museum of Vertebrate Zoology (MVZ) at Berkeley. One day in 1997 Eileen came home from work and said to John, “Hey, they have this picture of a database on the wall in the museum, and I don’t think anybody there understands it. Why don’t you go in and see if you can help them out?” John was initially doubtful, until she came home two weeks later to say the same thing. He recalls thinking, “Well, she’s going to do this until I go look at that damn database picture on the wall,” so he agreed to go in for a meeting a few days later. To his surprise, that meeting turned out to be an interview where he accepted a position to develop a modern relational database that would handle all of the collection data in the museum. He has proceeded to become a leader in the global effort to make informa-tion from natural history museums acces-sible to anyone with an internet connection.

Wieczorek is but one important player in the ongoing, interdisciplinary efforts neces-sary to get collections data online and in a central location. The standardization and centralization of specimen databases—docu-menting everything from large mammals to tiny insects and plants—is essential for understanding historical biodiversity and how it has changed over the past century

Movingnatural history

collections online

by Joan Ball

MA

REK

JAKU

BOW

SKI

NDigitizing the Drawers

Digitizing the Drawers

36 Berkeley Science Review Fall 2011 Fall 2011 37Berkeley Science Review

There’s a

MAPfor that

Cell phones for a better commute

by Ginger Jui

ERIC

FIS

CHER

ooking down and across the San Francisco Bay from the Berkeley hills during the evening rush hour, one sees an umbilicus of traffic—amber headlights on the left, ruby taillights on the right—stretching across the Bay Bridge, con-

necting the gridded East Bay streets to the skyline of San Francisco. A traffic engineer admiring this scene might ask: “Where are all these people going?” “Is traffic this bad everyday?” or “How can we make it f low faster and more efficiently?” Increasingly, the need for real-world solutions to traffic problems requires transcribing this bird’s-eye view of traffic information into actual hard data on a computer. This task requires ubiquitous technology allowing individuals to transmit information about their environ-ment, as well as the computational power to amass and analyze this data at break-neck speeds. Today, UC Berkeley researchers are merging the fields of civil engineering and information technology to bridge these information gaps between the traffic models on their computers and the drivers on the ground.

Real-time traffic information is a valuable commodity. For over 40 years, the major source of traffic information for the California Department of Transportation (Caltrans) has been loop detectors. These are the thick cables embedded as a circle or hexagon in the asphalt of highway lanes that are also commonly used to detect whether cars are stopped at stoplights. Historically, Caltrans invested in loop detectors because they report the three main pieces of infor-mation—traffic speed, volume, and occu-pancy—necessary for generating a complete picture of highway conditions. However, loop detectors are expensive to build, highly sensitive, and difficult to maintain, requiring Caltrans to shut down whole lanes of traffic if an array of detectors goes haywire. As California state budgets continue to shrink, Caltrans is looking for cheaper and more effective alternatives for gathering traffic information.

One such alternative is now available in the form of Global Positioning System (GPS) data from mobile devices. GPS data

L

20 Berkeley Science Review Fall 2011 Fall 2011 21Berkeley Science Review

A lab space of one’s own

The QB3 Garage: an incubator for innovation

by Susanne Kassube

EGG

NES

T: F

RIZZ

YCH

ICK;

DES

IGN

: VA

LERI

E O

’SH

EA

Fall 2011 29Berkeley Science Review

LEA

H A

ND

ERSO

N

s the story goes, University of Pennsylvania psycholo-gist Martin Seligman, a self-described pessimist, was weeding his garden

when his five-year-old daughter Nikki began playfully shrieking and tossing weeds in the air. As Seligman scolded her harshly for being disruptive, his daughter spun around, looked Seligman in the eye, and said: “Daddy, stop being such a grouch!”

Seligman says that he took this as a wake-up call. Being a pessimist was some-thing he could deal with, even something to be proud of in his academic circles, yet being called a grouch made him cringe. His research up to this point centered on the roots of depression, but the gardening incident made Seligman realize that he, and perhaps the field of psychology as a whole, had focused solely on negativity for too long. So, shortly after his appointment as president of the American Psychological Association in 1998, Seligman charted out a new approach for the field. Dubbed “positive psychology,” this branch of research would focus on human thriving over human pathology—studying function over dysfunction.

The movement quickly developed a fol-lowing, including at UC Berkeley. At around the same time, an entirely separate journey brought two Cal alumni, Tom and Ruth Hornaday, back to their alma mater. The Hornadays had recently dealt with a tragic family loss, and came to Berkeley in 2001 with the idea of funding multidisciplinary research on social and emotional well-being. After speaking with several Berkeley profes-sors already studying the positive psychology topics that they wanted to help promote, the

by Azeen Ghorayshi

The science behind positive psychology

The brain ishalf full

Hornadays created the Greater Good Science Center (GGSC).

Housed within the UC Berkeley Child Study Center on the south side of campus, the GGSC offers undergraduate and gradu-ate research fellowships, holds community lectures, and publishes the online Greater Good magazine to highlight current research in the field. With the belief that positive human traits are innate and strongly tied to individual thriving, the GGSC and its positive psychology peers hope to promote the elusive holy grail of personal achieve-ment—true happiness.

Our better halvesBefore the field of positive psychology could really get off the ground, it needed a mani-festo of sorts—a clearly paved vision for its new focus on positive human behaviors. To create the common language and standard-ized protocols necessary for a rigorous sci-entific discipline, Seligman and his cohorts wrote the Character Strengths and Virtues (CSV) manual—equivalent in purpose, but opposite in focus, to the Diagnostic and Statistic Manual of Mental Disorders (DSM) used to characterize psychological condi-tions for over 50 years. Psychology up to that point, said Seligman, had studied “only half of the landscape of the human condition,” and the CSV would thus serve as the DSM’s natural counterpart.

The manual lays out the central tenets of the positive psychology field. The main idea is that virtues such as compassion, courage, and wisdom are as much a part of our human nature as selfishness, weakness, or ignorance. Therefore, just as psychological illnesses need to be identified, treated, and prevented,

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Digitizingthe Drawers

Page 38: Berkeley Science Review - Fall 2011

36 Berkeley Science Review Fall 2011

There’s a

MAPfor that

Page 39: Berkeley Science Review - Fall 2011

Fall 2011 37Berkeley Science Review

Cell phones for a better commute

by Ginger Jui

ERIC

FIS

CHER

ooking down and across the San Francisco Bay from the Berkeley hills during the evening rush hour, one sees an umbilicus of traf-fic—amber headlights on the left, ruby taillights on the

right—stretching across the Bay Bridge, con-necting the gridded East Bay streets to the skyline of San Francisco. A traffic engineer admiring this scene might ask: “Where are all these people going?” “Is traffic this bad everyday?” or “How can we make it f low faster and more efficiently?” Increasingly, the need for real-world solutions to traffic problems requires transcribing this bird’s-eye view of traffic information into actual hard data on a computer. This task requires ubiquitous technology allowing individuals to transmit information about their environ-ment, as well as the computational power to amass and analyze this data at break-neck speeds. Today, UC Berkeley researchers are merging the fields of civil engineering and information technology to bridge these information gaps between the traffic models on their computers and the drivers on the ground.

Real-time traffic information is a valuable commodity. For over 40 years, the major source of traffic information for the California Department of Transportation (Caltrans) has been loop detectors. These are the thick cables embedded as a circle or hexagon in the asphalt of highway lanes that are also commonly used to detect whether cars are stopped at stoplights. Historically, Caltrans invested in loop detectors because they report the three main pieces of infor-mation—traffic speed, volume, and occu-pancy—necessary for generating a complete picture of highway conditions. However, loop detectors are expensive to build, highly sensitive, and difficult to maintain, requiring Caltrans to shut down whole lanes of traffic if an array of detectors goes haywire. As California state budgets continue to shrink, Caltrans is looking for cheaper and more effective alternatives for gathering traffic information.

One such alternative is now available in the form of Global Positioning System (GPS) data from mobile devices. GPS data from the smartphone in your pocket and

L

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38 Berkeley Science Review Fall 2011

navigation devices on your dashboard may revolutionize how Caltrans and UC Berkeley researchers track travel behavior and design transportation infrastructure.

Integration of mobile technologies into traffic monitoring and planning is a problem that sits at the intersection of aca-demic research and the public and private sectors. The California Center for Innovative Transportation (CCIT) attacks precisely this kind of problem by taking an innovative approach to the significant scientific, busi-ness, and deployment challenges it presents. A non-profit affiliate of the UC Berkeley Institute of Transportation Studies, CCIT works to bring cutting edge research from UC Berkeley to make transportation systems safer, cleaner and more efficient: in a word, more sustainable.

The mobile solutionJump to February 2008. One hundred cars driven by UC Berkeley students roll onto a 10-mile stretch of I-880 between Hayward and Fremont, California. Each car is identi-fied by a tarp taped to its hood numbering between 00 and 99 and carries in it a GPS-equipped Nokia cell phone. For the next eight hours, these intrepid students drive in loops on the I-880 while their cell phones transmit GPS coordinates back to a server at UC Berkeley.

engineers everywhere, Mobile Century was a scientific leap forward. It demonstrated that it was possible to build algorithms and data infrastructure to process cell phone GPS data in real time, and that these estimates of traffic conditions were accurate and reli-able. Following Mobile Century, the next crucial problem to solve was capturing more of the valuable GPS data riding around in everyone’s pocket.

As it turns out, there’s an app for that. Mobile Millennium—the next generation real-world experiment that emerged from Mobile Century—rolled out in November 2008. Rather than providing drivers with a particular cell phone, UC Berkeley researchers—with the help of Navteq, a location-based services company—rolled out a traffic application that drivers could download from the Mobile Millennium web-site. Mobile Millennium had two goals. The first was to incorporate GPS data reported by cell phones, as well as historical data, GPS from San Francisco’s taxi cabs, and data from existing radar and loop detector infrastructure into a complex traffic model to monitor traffic conditions on both high-ways and arterial streets. The second was to report this traffic information back to users. This app, the first traffic app deployed by Nokia in North America, was downloaded from the Mobile Millennium website by over

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Dubbed Mobile Century, this mass joy-ride was sponsored by Caltrans and involved CCIT, Nokia, and the UC Berkeley Civil and Environmental Engineering department. Mobile Century sought to demonstrate that cell phone-based GPS data could be used to accurately estimate traffic speed and trip duration in real time. While other research-ers had deployed this technology in highly controlled experiments, the Mobile Century experiment tested this concept in real-world traffic conditions for the first time.

Traffic engineers are giddy about the rise of GPS-equipped mobile devices. As Professor Alex Bayen, who is jointly appointed in the Department of Electrical Engineering and Computer Science and the Department of Civil Engineering, explained enthusiastically in a recent interview, “The big novelty in 2009 was that every cell phone,” waving at the iPhone I’m using to record our interview and the Android phone he pulls out of his pocket, “suddenly had a GPS, and that created an explosion of data. That opened a big opportunity for transportation because suddenly you could do monitoring in places where you don’t have dedicated infrastructure.”

That explosion of data could potentially be harnessed as a cheap and widely available data source for use in traffic monitoring, con-trol, and planning. For Caltrans and traffic

FEATURES Mobile tech

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Fall 2011 39Berkeley Science Review

5000 users during the twelve months of the experiment.

Developing a new marketMobile Millennium, in principle, served as a proof of concept for a traffic informa-tion product to help consumers plan their commutes using real-time traffic informa-tion. This idea has now been replicated, implemented, and marketed by a number of companies, including Navteq, Traffic.com, and Google Traffic. The success of Google, however, has driven the consumer-product based business model to extinction. “It is hard to sell a free commodity,” Professor Bayen quipped. “Because some websites give it for free, the market for travel information has dramatically shrunk in recent years.” Yet, in the face of Google’s grip on the traf-fic monitoring market, an innovative new business model is emerging from the Mobile Millennium research thanks to a continued collaboration between Caltrans and CCIT.

The CCIT office sits on the third floor of the former Masonic Temple in Berkeley, at the corner of Bancroft and Shattuck. The day I met Ali Mortazavi, program manager of the deployment and innovation team at CCIT, there was a blue Corvette convertible parked out front: a gas guzzling eight-cylinder sports car with leather bucket seats. Surprised, having assumed that the CCIT staff would be a more eco-friendly bunch, I asked Mortazavi whether it belonged to someone inside. He reassured me that it didn’t, and

that he himself commuted to work in a fuel efficient four-cylinder Hyundai.

Caltrans and researchers at CCIT are very interested in using mobile probe data collected from GPS-enabled phones and other dashboard GPS units. Currently, however, loop detectors are the only technol-ogy that provide all three crucial pieces of traffic data—occupancy, volume, and speed—needed by CalTrans’ traffic models. “Right now Caltrans installs sensors every half a mile,” says Mortazavi. “Now imagine you install sensors every mile or two miles, and fill in the gaps with [GPS] data. That would be a huge cost reduction.” Furthermore, rather than kicking out all of the existing traffic monitoring infrastructure, he says, CCIT and Caltrans are taking an incremental approach to assessing the added value of GPS data purchased from third party vendors.

The available GPS data is a heteroge-neous mix, coming from mobile consumer devices, GPS in commercial f leets (such as buses, trucks, and taxicabs), the San Francisco Bay area’s electronic toll collec-tion system, FasTrak, and radar. CCIT and Caltrans want to figure out whether the information they are collecting might allow them to decrease the number of loop detec-tors to install and maintain. In addition to the scientific work of building traffic models, Mortazavi and CCIT are also working on each step on the business side of deploying this cutting-edge technology, from design-ing the data specs, writing the terms and

conditions of data contracts and procuring the data. “We’re trying to create a win-win situation for both Caltrans, who would like to provide something beneficial for the public, and the private sector, who are looking for more profit,” says Mortazavi.

Significant scientific challenges are associated with the acquisition of more traffic data. There are different errors associ-ated with various measurement devices, and orthogonal types of information available from each technology. For example, one task for the algorithms being developed in Professor Alex Bayen’s lab is to fuse count and volume data from loop detectors with speed data from cell phone GPS. The end goal is to leverage both types of information to get a better estimate of traffic density. The problem is, Mortazavi explains, “it’s really easy to blend speed from different sources, but it’s really difficult to mix different data types, for example, volume and speed.” This challenge is now being tackled in Bayen’s lab, using what Mortazavi calls “fusion algorithms” for the different data types and in the traffic models that use this data to generate a real-time traffic map.

So far, it seems like the algorithms and models work pretty well. I dropped by post-doc Anthony Patire’s cubicle at CCIT to have a closer look at the traffic models. He has been at CCIT for less than a year, after getting his PhD in Civil and Environmental Engineering at UC Berkeley. Patire clearly keeps busy: the walls of his cubicle are lined M

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with cryptic, albeit neatly organized, labels headlining different projects, such as “MM” (that would be Mobile Millennium), “FHWA,”

“T01702”, as well as other titles like “Random” and “Fun Stuff.” His workstation is com-posed of two computer screens aglow with computer code and a groaning bookshelf that carries hefty titles such as Stochastic Processes and Non-linear Programming.

Patire pulls up what looks like a Google Maps-based web application to show me the Mobile Millennium traffic models running in real time. “The purpose here is to take real time data, run it through a model, and use the model to fill in gaps where we have no data,” he explains. “The model’s not perfect. Sometimes, it will predict something that’s just a little bit off. For those places that we have measurements, we can get it back on track.” In other words, the model is able to reflect traffic conditions in real time using a combination of real data and computer modeling. As Patire reports, “You would see a traffic jam form [in the Mobile Millenium app], and it could be 15 minutes until it is posted on other traffic monitoring websites.”

Noon on Wednesday looks like a good time to head into San Francisco: the real-time traffic map he pulls up shows all the major highways and arterial streets highlighted

traffic, now traffic, and future traffic.”Bayen explains: “Let’s say you want to

go from Berkeley to Mountain View. The simplest router is going to give you a route based on shortest travel time, assuming the posted speed limit. Because it’s smart, it’s not going to route you through the tiny roads, even though it might be faster on the map. It’s not, because of stop signs and pedestrians. In practice it’s going to route you by the shortest time through the freeway system, when it can. That doesn’t take into account traffic. The [second generation] routers account for historical traffic data; [it tells you,] don’t count on 20 minutes between San Mateo and the Dumbarton Bridge, you should count on 30 minutes.”

But what if there is an accident on the Dumbarton Bridge? Third generation routers will incorporate real-time traffic information to optimize your route. Bayen says, “You look at traffic now…and actually there is no traffic today, even though it’s 6 o’clock. Since there is no traffic, you’ll still use the freeway.”

Bayen’s master’s student Paul Borokhov is working precisely on this problem of the third-generation router. Borokhov is developing a smartphone app, tentatively titled the “Reliable Router,” that will use real-time traffic data to suggest routes that

in a “happy traffic” green. In fact, it looks very much like the map you would see if you clicked the current traffic conditions button on Google Maps—the Mobile Millennium map looks equally well connected and the coverage is quite extensive.

Moving forwardThe Mobile Millennium real-time maps are not yet available online to the public, but can be seen on display in the lobby of Sutardja Dai Hall on UC Berkeley’s campus. This building houses CITRIS, the Center for Information Technology Research in the Interest of Society, whose mission is to

“shorten the pipeline between world-class laboratory research and the creation of start-ups, larger companies, and whole industries.” Inside the lobby of the CITRIS building, there is a touch-screen TV displaying the Mobile Millennium traffic map. Patire sug-gests Friday afternoons are the best time for watching the Bay Area traffic mayhem.

The data algorithms and infrastructure developed in Mobile Millennium are now being used in Professor Bayen’s lab at CITRIS to develop next-generation traffic routers. Bayen describes how traffic routers currently fall into four categories of ascending sophis-tication: “zero notion of traffic, historical

FEATURES Mobile tech

Meet Mobile Millenium

Mobile Millenium is a groundbreaking project that asks a unique research question: can we use consumer technology to improve the real-time modeling and distribution of traffic information?

The first phase of this Caltrans sponsored project sought to use global position systems (GPS) in cellular phones to gather traffic information, model that traffic in real time, and broadcast the information back to users. This project was sponsored by Caltrans and the initial phase involved a public-private partnership between the California Center for Innovative Transportation (CCIT) at UC Berkeley, Nokia Research Center and NAVTEQ, a location based services company. In November 2008, CCIT launched the Mobile Millenium traffic app that was downloaded by over 5,000 users onto their Nokia cell phones. This 12 month pilot program provided a proof of principle that GPS data harvested from consumer devices could be used to successfully model traffic information in the Bay Area.

Today, the Mobile Millenium traffic model continues to run from a server housed at CCIT. It gathers traffic data from a large variety of sources, including cellular phones, GPS in commercial fleets (such as buses, trucks and taxicabs), the San Francisco Bay area’s electronic toll collection system, FasTrak, and radar. Students and researchers at CCIT and across the UC Berkeley campus continue to work on refining this data-modeling infrastructure. Because Mobile Millenium is a unique public-private partnership, this work includes both hard scientific questions and business-side development and implementation. CCIT is currently working to define and test business models for acquiring and distributing traffic information from private companies. Meanwhile, research work continues to improve the server-side hardware infrastructure to handle the increasing amounts of traffic information that needs to be processed and distributed in real-time. In addition, the modeling outputs are being used to generate unique traffic information products, such as graduate student Paul Borohkov’s Reliable Router traffic app.

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would maximize the probability of reaching a destination on time. For drivers, getting to a destination on time may be more important than getting there along a shorter or nomi-nally faster route that also comes with a high probability of lengthy delays.

The “Reliable Router” algorithm works by creating a network of alternative routes between point A and point B. It then uses real-time traffic information from the Mobile Millenium traffic monitoring server to estimate the probability of arriving at your destination on time for each alternative route. In order for the “Reliable Router” algorithm to produce the best possible route, the algo-rithm cannot give the full set of directions to your destination at the outset. Instead, the app gives a set of guidelines that update themselves as you drive. As you come to

a node leading to alternative routes in the network, the algorithm chooses the best next segment for your route based on the time remaining to travel to your destination and the updated traffic conditions along the alternative routes.

The instantaneously updated traffic directions in “Reliable Router” led Borokhov to develop a method for giving audio direc-tions on the fly. Borokhov explains, “When you’re driving, looking at street names is difficult. You have to figure out where the sign is, read the sign, remember which street you’re supposed to turn on, and then you’ve passed the street because you’re driving 45mph. The innovative thing is that we can tell people, ‘go right on the second street’, and it takes care of the problem of needing to know street names. You also minimize

driver distractions because these are audio directions.”

I asked Borokhov whether this app could be used to optimize for routes that minimized fuel consumption. He specu-lated that it could be done with a few modi-fications. For each link in the network, one could estimate the amount of fuel consumed along a given route based on the current traffic conditions and then optimize the route for fuel efficiency. However, Borokhov cautioned that to generate an accurate environmental impact estimate, one would have to avoid making overly simplistic assumptions about the vehicle and its rate of fuel consumption. By integrating robust models of vehicle emissions and real-time travel data, future travel behavior models developed at CCIT and CITRIS may enable unprecedented minimization of environ-mental impact for regional transportation networks.

Building this integrated network of mul-timodal transportation information poses the next significant challenge for traffic modeling algorithms. The use of data from mobile technologies, which can give granular information down to the level of individual people and their movements, will provide both the scaffolding and the substance for these algorithms as they enable the next level of interaction with our transportation system.

From linear highways to transporta-tion networksResearchers like Patire and Bayen can no longer regard highways as linear systems largely disconnected from smaller streets. While the earliest models, like the one used in Mobile Century, focused on highways, the next generation of traffic models must also address improving mobility in the arte-rial streets that feed these highways. As Ali Mortazavi at CCIT says, “You cannot draw a boundary here on the highway and not care about what’s happening in the arteri-als. Everything is connected. If you mess up something in one corridor, you’ll affect everything in the network. In urban areas, the congestion is high and if you shut down one thing you’ll affect everything.”

This network approach will be a sig-nificant scientific challenge. “The highway

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is easily mapped [using GPS] because it’s easy to when see someone is driving 60 miles an hour,” explains Mortazavi. “Now you have a lot more parameters. You have people walk-ing outside and inside buildings, and people stopping at traffic signals. That’s another challenge and it’s exciting.”

Future directionsToday’s transportation systems are complex networks populated by multimodal users. Everyone I interviewed for this article had a different way of getting to work—biking, driving, taking the commuter rail—showing just how many parameters the traffic engi-neer of the near future will have to account for in models of transportation network control and planning.

Real-time traffic information and mobile technologies could potentially nudge commuters towards more sustainable modes of transportation. CCIT is cognizant that traffic congestion cannot be solved by merely better monitoring and upgrading roadway infrastructure. Travel behavior itself must change.

palm-of-your-hand transportation data in applications like Mobile Millennium and Google Maps, this top-down approach to transportation communication aims to empower commuters with an incredible range of options to optimize their preferred mode of transportation.

With these systems in development, the focus now shifts to the way commuters will actually interact with the information with which they are presented. Will commuters optimize travel time or greenhouse gas emissions? Are drivers worried about fuel consumption or more subjective concerns like how relaxing, safe, or scenic their com-mute can be? By intersecting sustainability, technology, and transportation and informa-tion, UC Berkeley researchers are giving us, and the statewide agencies that set trans-portation policy, the tools and knowledge to start answering these questions to improve our daily lives.

Ginger Jui is a graduate student in integrative biology.

Caltrans is also increasingly in the business of influencing driver behavior, by giving real-time information on traffic congestion to help drivers predict travel time, plan alternate routes, or even choose to take public transit instead of using their vehicles. Caltrans and CCIT are already active in pur-suing this line of thought in a project you have probably seen on highways around the Bay Area: the deployment of the black and orange Changeable Message Signs (CMS) that give, for example, rush hour travel times from Berkeley to downtown San Francisco. CCIT has recently partnered with Caltrain, the commuter rail between San Jose and San Francisco, to add public transit information to these signs. During rush hour, signs along Highway 101 now compare drive times with riding Caltrain to work, hoping to nudge drivers to choose public transit for their commute. In addition, CCIT is currently developing another mobile app in collabora-tion with IBM, called “Smarter Traveler,” that will push commuters to take transit, walk, or bike even before they get into their autos. Combined with the vertically integrated,

FEATURES Mobile tech

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Movingnatural history

collections online

by Joan Ball

Digitizing the Drawers

Digitizing the Drawers

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atural history collections around the world contain over one billion specimens, and

could reveal important changes in biologi-cal systems that have occurred over the past 100–200 years. In the internet age, you might expect that specimen data would exist in online databases, but this is not the case for most museums. The painstaking endeavor to make natural history collections digitally accessible requires huge data entry efforts and the coordination of interdisciplinary teams of scientists.

Biologists of diverse disciplines are increasingly collaborating with computer programmers to create efficient data man-agement and dissemination systems. John Wieczorek is a programmer whose domestic partner, Dr. Eileen Lacey, happens to be cura-tor of mammals in the Museum of Vertebrate Zoology (MVZ) at Berkeley. One day in 1997 Eileen came home from work and said to John, “Hey, they have this picture of a database on the wall in the museum, and I don’t think anybody there understands it. Why don’t you go in and see if you can help them out?” John was initially doubtful, until she came home two weeks later to say the same thing. He recalls thinking, “Well, she’s going to do this until I go look at that damn database picture on the wall,” so he agreed to go in for a meeting a few days later. To his surprise, that meeting turned out to be an interview where he accepted a position to develop a modern relational database that would handle all of the collection data in the museum. He has proceeded to become a leader in the global effort to make informa-tion from natural history museums acces-sible to anyone with an internet connection.

Wieczorek is but one important player in the ongoing, interdisciplinary efforts neces-sary to get collections data online and in a central location. The standardization and centralization of specimen databases—docu-menting everything from large mammals to tiny insects and plants—is essential for understanding historical biodiversity and how it has changed over the past century

Movingnatural history

collections online

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or more. Dr. Stan Blum, a bio-diversity informatics specialist at the California Academy of Sciences, says that, “We’ve been beating the drum on digitization for a long time and it seems to be steadily gather-ing momentum. But you have to keep beating the drum,” to attract the investments needed for much larger collections.

The need to digitizeWith the advent of increasingly sophisticated technologies, the use of natural history collec-tions data has expanded from its traditional uses in taxonomy to studies in ecology, bioge-ography, pest management, disease transmission, conserva-tion, and more. Scientists are using methods in chemical and molecular analysis to measure contaminant levels in preserved specimens, determine food items consumed, and clarify evolutionary relationships derived from genetic data. Researchers can associate specimen occurrences and their attributes with geographic data on climate and land use. In this way, museums serve as repositories of valuable resources for understanding the biological effects of climate change and habitat modifications.

Collections are increasingly responding to the demand for data by creating open-access databases, available for easy search and download. Vertebrate collections in particular have become highly accessible through online databases. The MVZ at Berkeley is a driving force behind this trend. Not only was it one of the first museums to completely digitize and geographically reference its entire collection of around 677,000 specimens, but it has also been part of several multi-institutional collaborations that continue to digitize collections from around the world. The MVZ has gone so far as to digitize historical field notes, pho-tographs, annotated maps, gene sequences, and vocal recordings of frogs and birds. They

and money, and entomological collections have experienced dwindling personnel and funding.

The Essig Museum has recently launched a large effort to digitize 1.2 million arthropod specimens from eight institutions across California through a project called Calbug. Although it may seem late in the game compared to the MVZ, this is the largest effort so far attempted for insect collections in terms of specimen number, species number, and geographic area covered. If all goes well, the bees will catch up with the birds, bringing collections management and global change studies into the 21st century.

Some historical context The MVZ first managed their data on paper when vertebrate collections were established at Berkeley in 1908. From that time until the late 1970s they used ledger folios and card

are in the process of tagging and linking all of this auxiliary information to individual specimens.

On the other end of the data manage-ment spectrum, many collections have absolutely no means of searching specimen information from a central location. Most of these collections have simply been unable to muster the considerable resources required to digitize. Insects have particularly high diver-sity and very large numbers of specimens exist in collections, so the task of digitizing has seemed impossible. “By and large there has been no concerted, coordinated effort to get that huge amount of data digitized,” says Dr. Rosemary Gillespie, director of the Essig Museum of Entomology at Berkeley.

“People in Entomology collections have just thrown up their hands, because it’s such a huge quantity of data.” Digitizing collec-tions requires significant investments of time

A partial illustration of Arctos, the open source database that the MVZ uses to capture and store specimen information.

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catalogues to keep track of holdings, similar to the old catalogue system at public libraries. These cards and ledgers were used to locate specimens and find associated information such as date collected, locality, collector, and taxon name. Such lists provided a central place to look up information. The catalogues then became a valuable resource for effi-ciently digitizing the collections, eliminating the need to physically sort through specimen drawers and cabinets across the museum.

Digitization began in 1979 at the MVZ, when Berkeley ran on mainframe comput-ers. Faculty members and staff had access to keyboards and monitors, but no personal computer, and hundreds of individuals accessed a single mainframe. As Stan Blum, a former programmer with the MVZ, explains,

“They just plugged you in over the wire to the mainframe computer on campus.” The MVZ started digitizing mammals, reptiles, and amphibian records using the card catalogues, and then digitized bird collections directly from specimen labels. Concerted digitization continued until 1983, and included every-thing from the earliest specimen (a bird egg from 1843) to the most recent. Now, new specimens are digitized before they enter the collection.

Changes in computing technology became an impetus to revamp data man-agement at the MVZ, when in the early 90s the MVZ learned that the university’s mainframe computer, where they had cre-ated and managed their database, would soon be decommissioned. This system had already exceeded its capacity, and they had 32 different databases for the collection. They needed a better way to manage a growing body of data—a database that could handle all the information typical of natural history collections. This database should be capable of relating a variety of data associated with specimens, including the basics (taxon name, collector, date, location), and extras like field notes and photographs.

Blum originally entered the field of biodiversity informatics after receiving his PhD in Zoology. Blum says, “As a post-doc, I could see that the next curator position in Ichthyology wasn’t going to open up for another five years, and they come few and far between. In contrast, I knew the field of informatics was only going to grow.” For over CO

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Each individual specimen at the Museum of Vertebrate Zoology is linked to other types of media in the Arctos online database, improving the overall value and accessibility of specimen information. A search for this California condor egg, collected in 1907, turns up images associated with the specimen in addition the specimen record. Clockwise from top left: the California condor egg specimen; the egg’s original hand-written specimen label; nest site of condor; landscape around study site.

Specimen type: eggSpecies: Gymnogyps californianusCommon name: California condorContinent: North AmericaCountry: United StatesSpecific locality: 5.5 mi NE of PasadenaCoordinates: 34.201057°, -118.092905°Collecting Date: 10 Febrary, 1907Collector: Joseph Grinnell

Search results:

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twenty years he has been working full-time on projects that apply information technol-ogy to biodiversity science—helping museum scientists capture, manage, and efficiently analyze data.

In 1995 Blum came to Berkeley and cre-ated the mysterious “database picture on the wall” of the MVZ. He worked very closely with MVZ’s Staff Curator of Mammals, Barbara Stein, to create a roadmap for what would become the collection database. He did this using a methodology known as object role modeling. Blum needed to understand the ins and outs of all collection informa-tion and workflows to design an effective database. This methodology explored the combinatorics of data in detail, that is, how many entries can go into each field and how each field can and cannot be related to others. They spent a lot of time doing structured interviews, where he would ask about each different type of data at the museum and what concepts should be included. For example, they would discuss tissue samples by creating lists of all the possible tissue types, all the different vials tissues could be stored in, all the species with which they could be associated, specifying the number of possible entries for each field, and mapping

a programmer nightmares, but it is very satisfying in the end when the database is cleaned up.” Gross put the MVZ database online in 1999.

In 2005, Blum’s model was incorporated into the Arctos data-management system created by Dusty McDonald and Gordon Jarrell. With Arctos, users can search for and add information online through a web interface, which automatically populates the database. This is the open source software that the MVZ uses to manage its database today, along with collaborators such as the Museum of Southwestern Biology in New Mexico, the Museum of Comparative Zoology at Harvard and many others. The Berkeley model was also the basis for Specify, another open source program for biological collections data management, supported by the University of Kansas.

Increasing data sharing, accessibility, and valueThe critical step after digitization is what Wieczorek calls “data mobilization”—making the data readily available and increasing their value. Specimens of any particular species are generally dispersed among numerous museums, so it is important to make multiple institutions’ data available simultaneously. For the vertebrate collections, data would not come from a single warehouse, but directly from each institution using a Distributed Generic Information Retrieval (DiGIR)

out the potential relationships among the fields.

The final conceptual model consisted of multiple

figures and a companion document. A computer algorithm then converted

the model to a logical data structure for the relational

database. The result was a very complicated

set of tables. “There is no way to parse

something that big and complicated in a hierarchical way, you have to drill down in bits and chunks,”

he explains. He left the museum

after his design work was finished, but his

model remains the basis for databases that most natural

history collections use today, and is loosely called the “Berkeley Model.”

When Wieczorek came to the MVZ in 1997, the abstract work of model design was over and his job was to implement the data plan. He first had to extract 32 MVZ-databases from the mainframe and standard-ize all the different fields and data types. He integrated the information from these files into a modern database system for all of the specimen-data, along with auxiliary data such as sound files and field notes. Imagine organiz-ing the house of a compulsive hoarder, sorting through junk to find anything of value, creating piles, and putting it all into a logical place. According to Joyce Gross, a programmer for Berkeley’s Natural History Museums consortium, “this kind of work gives

FEATURES Natural history

Mammal specimens at the Museum of Vertebrate Zoology. The collection also includes birds, reptiles, and amphibians.

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protocol, developed in a collaboration between Berkeley, the University of Kansas, and the California Academy of Sciences. The basic idea is that a user submits a query from a web portal, the portal sends the query out to all the participating institutions via DiGIR, and results are compiled and sent back in the form of a table, map, or downloadable file.

The MVZ helped lead the three multi-institutional collaborations that used DiGIR to provide simultaneous access to collec-tions data online. The first was the Mammal Networked Information System (MaNIS), which originally consisted of 17 collections.

“Initially, there were a bunch of big name institutions that were skeptical. Some of them thought that digitization would never happen. Others said it sounded like a good idea but they weren’t ready,” says Wieczorek.

“Before the end of funding for the project, however, all of the big institutions were on the waiting list to participate, and all have since become valuable contributors.”

MaNIS was wildly successful in creat-ing new tools for data mobilization. They developed a method to standardize the process of geographically referencing text descriptions of specimen locations, and

accounting for potential error. The MaNIS institu-tions then implemented a bulk geographic ref-erencing effort after all collections data were entered into a database. Each institution claimed specific regions to geore-ference, generally those for which they had good geographic knowledge. UC Berkeley claimed California, for example. Then the institutions geo-referenced all collection points from that region no matter which museum the specimens came from. Wiezcorek’s eyes lit up when he explained how people liked this way of doing things. “They loved it. Collaborative georefer-encing created a commu-nity, because people from

different museums had to talk to each other when issues came up. The collaboration and the sense of community might have been the best thing that ever came out of MaNIS.”

Having georeferenced localities increases the value of museum data. Not only can users now get vertebrate data online, but they can also easily create distribution maps showing specimen localities. When the a collaboration later formed among 52 herpetology col-lections, produc-ing the HerpNET database, they had a successful example to follow, and were able to use the same collabora-tive georeferencing model, tools, and procedures.

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Georeferencing methods are now appli-cable to collections in general. After MaNIS, the Moore Foundation awarded Berkeley a collaborative grant of $1.6 million dollars to further advance georeferencing and to establish best practices. Under this grant Wieczorek created BioGeomancer, a work-bench and a web service to automatically georeference localities online. The last of the multi-institution digitization projects that the MVZ participated in was ORNIS, for bird specimens. ORNIS used BioGeomancer to double the speed of georeferencing. The MVZ now gives extended international workshops on georeferencing to train students, researchers, and collection staff, on campus and elsewhere, on the standard concepts and procedures.

The MVZ is now working to tackle the problem of sustainability. There are not currently enough resources to keep up with the demand of institutions that want to get involved in MaNIS, HerpNET, ORNIS, and their sister vertebrate network, FishNet. The MVZ, under principal investigator Carla Cicero, just received an National Science Foundation grant to create and coordinate VertNet, which would combine data from all the vertebrate disciplines. The goal is to streamline the process of data publish-ing, remove the need for

FEATURES Natural history

Pinned beetle (opposite page) and wasp (right) specimens. The pin or angle of the label can potentially obstruct important information, which is sometimes hand-written.The imaging process for specimens like this takes considerable time and effort.

A researcher at the the Essig Museum of Entomology displays one of hundreds of specimen drawers waiting to be digitized. The drawers are tightly packed with insects, averaging 200 specimens each.

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participating institutions to maintain their own servers, and increase the performance and capabilities of the networks under one cloud-based platform. Though early in the project, Wieczorek and colleague Aaron Steele are confident that the 176 participating collections and the waiting list of 61 more can all be transitioned into the new VertNet within the first year and a half of the three-year project. The economic impact will be

an estimated 20-fold reduction in the cost of maintaining the network.

Potential new approaches for large Entomology collections The question now is whether the models provided by past and ongoing efforts on the smaller vertebrate collections are trans-ferable to the enormous amount of data associated with invertebrate collections. Digitization projects for entomology collec-tions face incredible challenges, despite the helpful precedents from the MVZ and other vertebrate collections. The Essig museum at Berkeley alone has more than 6 million specimens in its collection. Calbug has an NSF grant to digitize 1.2 million specimens from collections across California using methods similar to those from MVZ’s digiti-zation efforts. While this is one of the largest attempts to digitize arthropod collections, it

them together to create a single high-reso-lution image. With the final mosaic image, one can then zoom from a large picture of the entire drawer of 200 insects to the tiny hairs on the leg of a single specimen.

Drawer-scanning technology has not been applied to insect labels, but instead to high-resolution images of the specimens themselves. Obtaining data from labels is more difficult. Multiple stacked labels rest

below the specimens, containing useful information on the time and place of collec-tion. Essig staff still must arrange specimens so that all labels are visible, a process that is extremely time consuming when working with large numbers of samples. One potential benefit of scanning drawers would be to sim-plify workflow by eliminating the necessity to shoot single photos of specimens and save individual files manually.

The British Museum of Natural History has partnered with Smart Drive Ltd. to create the SatScan tray scanner and to develop software that can crop images of individual specimens and save files automatically using standard filenames. GigaPan is a similar technology, developed by the NASA Ames Research Center, Google, and the Carnegie Mellon Museum of Natural History, that uses a camera mount suitable for high-resolution cameras to take photos automatically from

is only a small fraction of the specimens in California collections.

Unique challenges associated with insect specimens compound the problem of huge collection sizes; specimens are small and delicate, and the labels are tiny and dif-ficult to read. The labels and specimens also have pins sticking through them, obscuring information. For these collections, the Essig team must find a way to mass-process data

from specimens and automate portions of the current workflow.

One approach that Calbug has been experimenting with is taking photographs of individual specimens in the collection, so that students and volunteers can enter data from images. It takes a significant amount of time to arrange specimens and labels such that all of the labels stacked on a pin beneath the specimen are legible. Peter Oboyski, a postdoc working with Calbug, envisions a Ford-style assembly line with a designated station for specimens that is set up for efficient image capture.

Essig staff are experimenting with new imaging techniques and methods to simplify workflow during the image-capture process. One option is to capture high-resolution images of entire drawers. Drawer-scanning technology takes multiple images from various angles across the drawer and stitches

1939 founding year 1908

1 full-time staff 13

142 oldest specimen age 175 56,000 number of species 18,200 6,000,000 number of specimens 677,000

2% amount digitized 100%

Museum of Vertebrate Zoology

Essig Museum of Entomology versus

FEATURES Natural history

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different angles throughout a drawer and software to stitch the images together.

The goal for all of these efforts is to increase the current production rate of 5,500 images every two weeks to at least 12,000. Essig staff are testing different methods to identify the most efficient one. Undergraduate students are essential to car-rying out this work; as Oboyski put it, “Most projects on this campus would never get done without undergraduate help. They are the unsung heroes of research on campus.”

The Calbug team plans to use specimen images together with large-scale approaches, such as crowd sourcing and automatic text recognition, to put the data into a useful structure. They are planning to collaborate with the Citizen Science Alliance, an organi-zation that has been very successful in devel-oping web interfaces for citizen science proj-ects. One of their projects involves digitizing

weather logs from Royal Navy ships around the time of World War I; on launch day of the project they had 100,000 pages digitized. The crowd-sourcing approach provides a mechanism for hundreds or thousands of people to do data entry work and to learn about collections and global research at the same time.

It may also be possible to develop opti-cal character recognition (OCR) software to interpret information automatically from insect labels. Current OCR software does not recognize the type of information on insect labels, including handwriting, type-face, and various abbreviations for the same word (California might be CA, Cal, or Calif). Calbug would have to build a dictionary of all possible abbreviations for words that may be found on the labels. They are working on this dictionary to further explore the possibil-ity of creating OCR software and to create

lookup tables for citizen science data entry. Following in the footsteps of the MVZ,

and benefitting from the technologies already developed, the Essig museum may become a leader in digitization of larger invertebrate collections. If successful, they will increase the scale of data capture by orders of magnitude. This would pave the way for collections throughout the world to digitize massive numbers of specimens. Each specimen, each drawer, each taxonomic group, and each of the natural history col-lections has the potential to add something important to our understanding of the flux of biodiversity. The combination of collections from around the world will hopefully lead to profound new insights.

Joan Ball is a graduate student in environmental science, policy, and management.

Eran Karmon Editor’s Award

In memory of Eran Karmon, co-founder and first Editor in Chief of the Berkeley Science Review.

This award is given annually to the Editor in Chief of the BSR thanks to a generous donation from the Karmon family.

FEATURES Natural history

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52 Berkeley Science Review Fall 2011

I was eager to open my copy of The Instant Physicist when it arrived. It was hard-bound, colorful, and best of all, skinny.

With time always at a premium, a short volume that promises to help you learn aston-ishing facts, win arguments with friends and relatives, make crazy-sounding bets and win money in less than 150 pages sounds to good to me.

The book is written by Berkeley physics professor Richard Muller, whose popular class “Physics for Presidents” won best class two years in a row, and humorously

illustrated by Joey Manfre. Each two-page entry consists of a colorful cartoon on one side and less than a page of writing on the

other, making this an ideal book to pick up for only a moment or two at a time. After thumbing through the first few pages, I already felt smarter for my newly-gained knowledge of the easy-to-digest tidbits Professor Muller presents.

After a few days of sporadic reading, a curious thing happened; I began to reference the information I learned from the book, often. It is amazing just how easily arcane physics knowledge can be woven into day-to-day conversa-tion. And when one of my pedantic friends started to read the book, he took the information and ran with it, holding multiple campfire audiences captive.

Some entries were fascinating and stood by themselves; some entries, however, left me hanging. I wanted more than the short entry and corresponding cartoon provided, and feared that the (sometimes

shocking) snippets of information could be misinterpreted if extrapolated upon without additional influencing factors. One that hit me particularly hard was the entry about organic foods being more toxic than their pesticide-controlled counterparts due to the fact that the naturally occurring insect resistance selected for in organic plants are thousands of times more carcinogenic than the pesticides used in conventional agricul-ture. While I understand this logic, I am not quite ready to give up my eating habits based on a picture of a fly slapping a poison sticker

on a barrel full of organic apples. But it did get me thinking, and perhaps that is what The Instant Physicist does best: providing food for thought and presenting a slew of quick facts that causes an inquisitive mind to question conventionally held notions or seek further data on arcane snippets.

Some entries also felt more silly than fascinating. It is interesting that a gram of chocolate chip cookies contains more energy than a gram of TNT, but the com-ment about giving chocolate chip cookies and sledgehammers to teenagers being more effective at destroying a car than blowing it up with TNT provides more silliness than knowledge. Then again, the book is about showiness as much as it is about the phys-ics, and that is partly what makes the book enjoyable. There are plenty of dry volumes without cartoons and silliness to go around; why not allow this book to be over the top? I particularly enjoyed the entry about Pluto’s revoked planetary status. Who does give the International Astromical Union (IAU) the right to decide on a status that is older than the organization itself? Congratulations, Dr. Muller, for reinstating Pluto’s planet-ness with a 512 to 0 classroom vote. Despite the occasional groan or roll of the eyes, this book gives exactly what it promises: instant physicist status.

Erin Jarvis is a graduate student in integrative biology.

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physWannabe

physWannabe: Did you know that alcohol must be radioactive to be sold?plebius: What?physWannabe: Yes... [explanation from The Instant Physicist and a few other random facts]plebius: Wow, that’s amazing! You should start a blog or something.

x

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Fall 2011 53Berkeley Science Review

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54 Berkeley Science Review Fall 2011

graduate experience was receiving a key to the department’s calculator room, which housed the expensive and large devices of the day. At Berkeley, De Valois was the second female faculty member in physi-ological optics (as vision science was then known), and served as chair of the psychol-ogy department from 1998–2003. At the 2010 vision science group retreat, De Valois gave an eye-opening keynote on the history of women in vision science, inspiring the creation of cross-departmental “Women in Vision Research” meetings to discuss barriers, mentorship, and career issues.

AA: What got you interested in color vi-sion? Are you an artist?KDV: A very bad one, only for fun! There are a number of things about color that I think make it particularly interesting. One, a trivial point, is that it’s beautiful; it makes the world more interesting to look at. More importantly, although color vision certain-

aren De Valois knows the ben-efits—and pitfalls—of scientific collaboration. During her three-decade career as a Berkeley

Professor of psychology and vision science, questions about her research were often directed to her husband, collaborator, and fellow professor, the late Russell De Valois. Though she worked for a decade as an inde-pendent principal investigator and adjunct professor through Russell’s lab, she eventu-ally became a professor in her own right in the early 1980s, establishing a research program that investigated human and animal color vision. While she may be best known for Spatial Vision, a cornerstone text in the perception field co-authored with her husband, she estimates that they collaborated on only two experimental publications over the first 20 years of her career.

Originally from Georgia, De Valois completed her psychology PhD at Indiana University in 1973. A highlight of her

ly is not necessary for life, or for survival, it is of all things in vision, or any sensory sys-tem, or indeed any behavior, the one area in which we may be likely first to understand the relationship between behavior and the underlying physiology. It’s that question that really drives me. Once we really un-derstand that, then that opens up a world of possibilities. If we truly can understand the biology as it’s related to the behavior, then we have done something really remarkable.

AA: How would you advise young re-searchers to approach scientific collabora-tion?KDV: There are many virtues to col-laborative research, particularly as things become more complex; we need to collabo-rate with people whose expertise is in ar-eas other than our own. There is, however, a danger in doing so. If you are a young faculty member trying to get tenure and your name comes out on lots of papers but

f a c u l t y p r o f i l e

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they’re all collaborative papers, particularly if you published with other scientists who are senior to you, then no matter where your name is on the list of authors, you will not get the same kind of credit for it. So collaboration is a great thing, but you have to make sure that you as an individual are given adequate credit. And I don’t think there’s any evil intent: it’s a legitimate ques-tion, but it’s going to very hard to get the credit that you need when everything you do is done in collaboration with someone more senior. This is why I encourage young faculty members not to continue publish-ing with their advisor for very long. You can go back and do it again later. You have to develop your own independent strain of research, which is very hard if you are still publishing with your advisor, after you have your own lab.

AA: Did you face these problems in trying to distinguish your research from your husband’s?KDV: Very much so. We made a decision early on, although he did both physiology and psychophysics, and I did too. We de-cided to split the two: I would primarily do psychophysics, he would primarily do physiology. This way, we could establish a

degree of independence. It was a practical choice, too. During those years I had very young children, and physiological experi-ments don’t stop at certain times. Even so, there were still people who would ask Russ in my presence about work that I had done, that he was not involved in. He would al-ways respond, “I don’t know, I wasn’t a part of that, ask Karen.” I established an inde-pendent research program, and although our interests were similar, we worked on unrelated questions. Much later we got to the point where we felt like it was ok for us to collaborate again.

AA: Has teaching also been a big part of your career?KDV: I taught a proseminar for graduate students in vision, advanced undergradu-ate classes in vision, undergraduate bio-logical psychology, and visual sensitivity for optometry students. I always enjoyed teaching about color or spatial vision. Peo-ple can relate immediately, because we’ve all experienced it. For one of my last lec-tures, I colored my hair hot pink! It sur-prised the class; I got a round of applause at the end.

AA: How has the practice of science changed since you were a graduate stu-

dent?KDV: I’ve been fortunate to be

in science through a period of just extraordinary techno-

logical innovation. In my first year as a graduate

student, one of the re-quired courses was electrical design and wiring. You could put individual logic gates in a rack, wire it up, and have some-

thing like a primitive computer. Before that we had to punch paper tape. By the time that I graduated there was a mainframe computer on campus. A few years later, Russ and I got our first tabletop calculator, a Hewlett-Packard. It was so expensive that we had it in a steel case chained to a desk. That year we also got our first lab computer. It had eight kilobytes of memory. We pro-grammed in machine language. Gradually, as computers came online it became pos-sible to display more complex imagery [for visual experiments]. The whole field that I worked in—color and pattern, spatial vi-sion—would not have been possible before the advent of computer displays.

AA: In your talk on the history of women in vision science, you mentioned a pio-neer in the field, Christine Ladd-Franklin. How have attitudes to women in science changed?KDV: When I was a graduate student, there were about 40 faculty members in my department. There were, by formal design, no women faculty. It was shocking to me to be told that the women admitted to gradu-ate school had to have substantially better records than the men did. Female graduate students were not recommended for jobs at major research universities; they were ex-pected to teach at small colleges. Both the law and cultural attitudes have made these issues less of a problem. Now we have time off the tenure clock, child care, but some-times institutions tend not to be particular-ly supportive. I really was fortunate to have a husband who understood and was very supportive, but you shouldn’t have to have that. The story of Christine Ladd-Franklin, who was denied her PhD by Johns Hopkins for 43 years, is very instructive in a lot of ways. She was never given the recognition that someone else in that situation might have received. It really does show how far we’ve come, not that we don’t still have ways to go.

Amanda Alvarez is a graduate student in vision sciences.

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M athematics has a reputation for being exact. Consider the Pythagorean Theorem, which

exactly relates the lengths of the three sides of a triangle. I didn’t know Pythagoras (c. 500 B.C.E.), but I like to imagine him scur-rying back and forth around a giant marble triangle, measuring the sides with a piece of string and chiseling the values into his granite lab notebook. When he sat down to ponder over his results, what did he make of his measurements? Specifically, what did he make of the fact that each time he went to measure side number one, he got a slightly different number? As it turns out, Pythagoras was something of an idealist. By ignoring the imperfections in his measurements, he gave us the beautiful and precise formula we love. However, another story lies in exactly that which Pythagoras overlooked: uncertainty. Probability and statistics are the branches of mathematics that embrace uncertainty and the fact that in the real world, we acquire all of our knowledge through imperfect measuring devices.

Historically speaking, probability and statistics were a bit late to the party. It wasn’t until 1654 (for those keeping track, that’s a mind-blowing two millenia after Pythagoras) that all-star mathematicians Blaise Pascal and Pierre de Fermat teamed up to give uncertainty a mathematical treatment. This lag is reflected in the types of mathematics that are taught last and remembered least in American schools (a recent survey by

the National Science Foundation showed that 43% of Americans lack an understand-ing of probability, a figure that only 57% of Americans grasp, unfortunately). Most current-generation traffic routing algorithms are Pythagoras-like in that they ignore the fact that measurements have variability—each time you drive down a road, it takes a different amount of time. The figure below shows what the full dataset might look like for two fictional roads, with the height of the curve at each point showing how likely it is for any one trip to last that particular amount of time. This chart is known as a probability distribution. A Pythagoras-like algorithm would assume that the road has one travel time—this distribution’s expected value, which is simply the average for all the trips observed (the dotted green and black verti-cal lines). This simplification might speed up the calculations, but we throw away any information we had about how dependable (that is, uncertain) the estimates are.

To better appreciate the devastating repercussions this might have, imagine you have to be home in 10 minutes to take a pie out of the oven. You can choose one of two routes, shown in the figure below. Option one is Bieber Speedway, a high speed express-way, which happens to also cut through the Justin Bieber Wax Sculpture Park, so that the occasional walking tour crosses the street and holds up traffic. Option two is the tranquil and secluded Country Road, which has a lower speed limit, but no Bieber Park. A

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current-generation router would only know the expected values (dotted lines) of both distributions: on average, Bieber Speedway gets you home in 6 minutes, which is faster than Country Road, which takes 8 minutes. Accordingly, the algorithm would direct you to take Bieber Speedway. It turns out that today just wasn’t your day, and a mob of fans crosses the street, adding 5 minutes to your trip. You get home to find that your pie is a sooty heap.

Closer inspection of the two probability distributions reveals how understanding uncertainty could have saved your dessert. By collapsing the entire travel time distri-bution to one number, traditional routing algorithms lose sight of the fact that a con-siderable proportion of trips down Bieber Speedway take longer than 10 minutes. Based on historical traffic data, there is a zero per-cent chance of a trip down Country Road taking 10 minutes or more, so while Country Road is slower on average, it is more reli-able. Next-generation algorithms like those employed in the Reliable Router (There’s a map for that, pg. 36 of this issue) keep track of the travel time probability distribution, allowing the reliability of each road to factor into your route selection.

Humans intuitively evaluate the uncertainty in life without much prompt-ing, which is why when you ask for direc-tions from a local, they’ll probably send you through low-risk routes. Computers are blind to these subtleties—until we

teach them. By endowing computers with the ability to appreciate uncertainty via the mathematics of probability and statistics, we come one step closer to automating good advice. Maybe a future genera-tion of algorithms will also favor routes that take us right by the best slice of pie in town.

Robert Gibboni is a graduate student in neuroscience.

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