Scalability CS 258, Spring 99 David E. Culler Computer Science Division U.C. Berkeley.
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Spring 2011 Issue 20
sciencereview.berkeley.edu
Illuminating
the dark genome
44 Not easy being greenFrogs swamped by asex-warping pesticide
26 Mud volcanoesAn eruption withno end in sight
21 Crib confidentialBabies reveal theirstatistical prowess
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Spring 2011 1Berkeley Science Review
Editor in Chie
Greg Alushin
Editors
Allison Berke
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Managing Editor
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Web Editor
Anna Goldstein
Web Designers
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PrinterSundance Press
Dear readers,
Wlcom to th 20th iu of th Berkeley Science Review nour tenth anniversary. To celebrate, I decided to rummagebck though ou chiv n pn om tim with Iu1. It w mkbl to how littl h chng, incluing,coincintlly, n nuing fcintion with volcno (Iu1 p. 7, Iu 20 p. 26), homonl gultion of xul bhvio(Iu 1 p. 5, Iu 20 p. 9), n ol tom (Iu 1 p. 4, Iu20 p. 6), phnomn which will continu to fill Bkly lband our pages for many years to come. Nevertheless, I am veryproud to say that we have come a long way from the black, white,
n blu of th fit ition. I woul lik to ict thi iuto the memory of Eran Karmon, our founding Editor in Chief,
who, by tting cinc mgzin tht nyon on cmpu coul pick up n njoy, plnt which h inc flow into n xpning voic fo ch with ch f byonBncoft n Ht.
A cinc wit, w pi to communict complx i ffctivly, hoping to inc thimpct of cinc in ocity. L oftn coni influnc going in th oth iction,yet the interplay between personalities, politics, economics, and research takes center stagethi iu. On pg 44, Sii Chn n Mk DWitt chonicl th c-long tuggl ovth ffct of ptici btwn contovil pofo, Tyon Hy, n th chmiclcompany Syngenta, waged through experiments, regulatory agencies, and personal vitriol.Kith Chvll ocumnt th mning cintific vinc tht n oil compny cu thcontinuing uption of th vtting Lui mu volcno in Inoni (p. 26) Finlly, on pg
60 Jacques Bothma makes the case for why Professor Michael Eisens dream of a scientificlittu f fo vyon to cc houl, n i, bcoming lity.
Th BSR i un by tunt who lo hppn to b cintit, n thu it i no upi thtwe continually tinker with (and sometimes dramatically alter) the form and content of ourmagazine. While we always have an opinion of what works best, I am pleased to announcea new way for you, our readers, to have a say: the Readers Choice Award, to be given eachiu. Go onlin (http://cincviw.bkly.u) to vot fo you fvoit ftu o bif;th utho() of th winning ticl civ $150 ch piz n pofil on th BSR blog,which i ly chock-full of wonful pic to kp you infom btwn pint iu. Inition to highlighting pticully tong wit, piz-winning ticl wil l inpi fututoi lvnt n intting to you.
A I hng up my ito ht, I woul lik to thnk l l of th wit, ito, n lyout tff fomking th pt y uch wonful xpinc n fo two iu tht highly pi pof-ionl (by jounlit tn, t lt) woul b h-p to bt. It h bn n hono.
Enjoy th iu,
Gg AluhinEito in Chif
from the edito rberkeley
Spring 2011 Issue 20
sciencereview.berkeley.edu
Illuminatingthe dark genome
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2 Berkeley Science Review Spring 2011
14 Reading between the genesCharting a course through the dark genomeby Azeen Ghorayshi
21 Baby labHow we learn to learnby Jacqueline Chretien
26 Drowning in mudScientists confront an ongoing eruptionby Keith Cheveralls
44 Murky watersScience, money, and the battle over atrazineby Sisi Chen and Mark DeWitt
53 Perchance to dreamUncovering the role of the unconscious mindby Naomi Ondrasek
60 Access grantedUnlocking the scientific literatureby Jacques Bothma
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 2010-2011 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 Universit y of California (ASUC), and the Eran Karmo n Memorial Fund. Berkeley Science Reviewis not an official public ation of the University of California, B erkeley, the ASUC, the GA
Lawrence Berkeley National Laborator y. The views expressed herein are the views of the writers and not necessarily the v iews of the aforementioned organizations. All events sponsored by the BSR are wheelchair accessible. For more information [email protected] to the editor andstory proposalsare encouraged and should be emailed [email protected] posted to the Berkeley Scien ce Review, 10 Eshleman Hall #4500, Berkeley, CA 94720. Advertisers:[email protected] visitciencereview.berkeley.e
c o n t e n t s
14
21
60
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Spring 2011 3Berkeley Science Review
1 From the Editor
4 LabscopesTouchy feelyby Mohan Ganesh
The sight of sound
by Monica Smith
Wireless water
by Sharmistha Majumdar
Winey pests
by Molly Sharlach
66 Faculty profileMina Bissellby Adrienne Greene
68 Book reviewKids FirstProfessor David L. Kirp
by Joseph Williams
69 ToolboxInformation theoryby Robert Gibboni
Spring 2011 Issue 20
COVER: Histone proteins (yellow), the spools around which DNA (green) is wrapped, arecritical for turning genes on and off. The modENCODE project is generating genome-wide
maps of dynamic chemical marks (red) on the histones to uncover the r ules that allow ananimal to develop from a single cell.
6 Sun stormsModeling solar phenomenaby Alireza Moharrer
8 Whats the antimatter?Probing the origins of theuniverse with antihydrogen
by Denia Djokic
9 Hormonal hassleHow stress can hurt your sex driveby Michael Cianfrocco
10 Its a bird... its aplane... its a robot!Machines that fly themselves
by Claudia Avalos
12Smart circuits
Making electronicsthat remember
by Chris Holdgraf
departments
berkeley
current briefs
26
6
53
CloCkwise from top-right: NAsA; pAul sApiANo; steve Axford; mArek JAkubowski; Joe kloC; mArek JAkubowski
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Evy y w u ou n of touch to gui ou wy though lifwithout giving it con thought. Engin hv long ought
to plict th complx n of touch in lctonic componntto give robots and, eventually, prosthetic limbs the same ability tointct with th uouning wol. A goup of lcticl ngint UC Bkly hv m ignificnt bkthough in th puuit ofproducing a sensor similar to human skin in its ability to detect pressure.
Pofo Ali Jvy n hi tm fbict vn qu cntimtsensor array using inorganic semiconductors cal led nanowires mounted
onto flexible, pressure-sensitive rubber. Previous electronic skins used
flexible organic components that were 50 times smaller in area andqui lg btty to povi th voltg n to opt thm.Jvy goup int opt to u nnowi tht qui mll volt-g. Pviou ch uing nnowi w limit to uing ingl
nanowire transistors on a very small sca le, says Dr. Kuniharu Takei, apostdoctoral scholar in Javeys group and lead author of the paper. The
sensor makes use of an innovative contact printing technique pioneeredby the team to mount hundreds of nanowires onto the sensor. Theelectronic skin is durable, making it ideal for future applications, whichJavey explains can range, from obotic, to giving g piplinth bility to lf igno the formation of cracks, andone day even interfac- ing with pothtic limb.
-Mohan Ganesh
-Monica Smith
Although cintit oftn wnt to look t vy tiny thing, it i tho-ticlly impoibl to omthing mll thn th wvlngthof th ition u to img it. In o to obv vn mll
objct, on coul ith u hot wvlngth, fo intnc bmof X-rays instead of light, or play a number of tricks to get around
this limit. The same principles that restrict the ability to resolvedetails in optical imaging also hold true for methods that use
soundwaves like ultrasound. Jie Zhu, a postdoctoral fellow inProfessor Xiang Zhangs lab at UC Berkeley, and colleagues
recently engineered a device capable of imaging objectsmll thn th wvlngth of oun u to ct th
acoustic image. The device has very small, square holesill though block tht ct pfct ln fo
transmitting sound waves. When waves with theproper wavelength hit an object on one side of
th block, infomtion contin in tningwv tht only xit vy clo to th objct
i fithfully tnf though th vic. Amicrophone placed close to the output of the holey
material can detect features up to 50 times smaller thanth wvlngth mitt by th ouc, vn tim btt
thn th bt olution pviouly vilbl. Thi tchnology
coul pwn th nxt gntion of pob fo micl onogphyn th non-tuctiv vlution of mtil.
C
loCkwisefromt
op-left:AliJAveyANdkuNihArutAkei;NextdropteAm;
l a b s c o p e sTouchy eely
The sight o sound
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Spring 2011 5Berkeley Science Review
In mny vloping counti lik Ini, unning wt i ccand only intermittently available. To tackle this challenge, UC
Berkeley graduate students Thejo Kote, Emily Kumpel, and AriOlmo, lunch ocil ntpi cll NxtDop in th fll of2009, with advice from Assistant Professor Tapan Parikh of the School
of Information. NextDrop aims to address the problem of unreliablepiped water in India by exploiting the ubiquity of cell phones inthe country. Mobile phones are everywhere, explains Kumpel.
Theyre a very easy way to get information to people. Local familiespticipt by ning txt mg to NxtDop oon wt
bcom vilbl. A n incntiv, th fit t of cll civ micopymnt. NxtDop thn vifi th ccucy of th wtlivy upt n immitly n txt to ll it ubcibin the same neighborhood. Since its modest beginnings as a class
pojct, NxtDop h gon on to win UC Bkly 2010 Big Icomptition n gnt fom th Gt Fountion n th ClintonGlobal Initiative. In July 2010 they began their first pilot program inth outhn Inin town of Hubli, with 200 fmil i wll th
local water utility board participating. In the future, NextDrop hopesto u livy t ccumult ov tim to pict whn wtwill iv in p ticul loclity, thby mpowing conumto ctivly pticipt in impoving vitl utility.
-Sharmistha Majumdar
-Molly Sharlach
Whn you think of th Np n Sonom Vlly, you pobbly imgin olling hill on with ow upon ow of ucculnt gp
vin-ipning in th un. Howv, bnth thi iyllic xtio th bctiumXylellafastidiosa i wking hvoc on Clifoniwin gp. By cutting off wt tnpot though th plnt,Xylella cu lv to with n fll off, ultimtly killing nti
vin. In n ffot to btt untn th mchnim of thi i, Aocit Spcilit Cll i Bcci n Pofo Stvn Linow ofth Dptmnt of Plnt n Micobil Biology tuying th movmnt of th bcti though th tiu of itnt n ucptiblgp viti. Thy u tin tht xp gn f luocnt potin, mking th bctil cll y to viuliz un micocop.Th plnt y cll pp , n btwn thm xylm vlwt-tnpoting vcul tiu. Th bight yllow-gn onth wll of th xylm full of bcti. D. Bcci foun tht ucptibl viti, uch Cbnt Suvignon on th lft, h bout
fiv tim mny infct xylm vl th Tmp gp, on th ight, which i ltivly itnt to th i. Cunt hypoth to why om gp viti mo itnt inclu iffnc in p compoition n th pouction of tylooutgowth of clluouning xylm vl, which my block bctil movmnt though th plnt.
Wireless water
Winey pests
Cabernet Sauvignon (10x) Tampa (10x)
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Sun stormsModeling solar phenomena
Every second, five million tons of matter
are converted into energy deep within the
Sun. Nucl ction in th co povi
the source of the Suns energy, which then
radiates through the dense interior and exits
through the Suns surface and atmosphere
into space. Along with this radiation, the Sun
mit vibl tm of chg pticl
f to th ol win. With p
of up to 2.5 mill ion mil p hou, th olwind blows past Earth and eventually escapes
our solar system. During active periods,
however, large magnetic eruptions called
flares or coronal mass ejections (CMEs) can
ticlly lt th ol win in wy tht
can greatly affect the Earth s geomagnetic
nvionmnt.
The enormous electromagnetic eruption
of a CME can interfere with our communica-
tion n lctic pow inftuctu. A
better understanding of how CMEs affect us
on Earth is necessary to ensure their integrity.Ou plnt h it own mgntic fil tht
ct gint potctiv bubbl, hiling
u gint th incoming ol win, but it i
not lwy n impntbl bi gint
a CME. An enhancement in the northern
light i mong th viul ffct of uch
disturbance, but charged particles associ-
t with CME cn hv oth, potntilly
destructive consequences. They can interfere
with th noml option of io n t-
ellite communications and electric power
gi, wll iupt globl poitioning
networks. Magnetic disturbances associated
with CMEs have occurred throughout his-
toy, with th tongt gomgntic tom
in cnt mmoy occuing in Mch 1989.Over the past decade, a team at UC
Berkeley, NASA, and other concerned indus-
ty ptn, hv bn woking tow li-
bl mol of CME tht coul vntully
v focting tool. Th collbotiv
Solar Multidisciplinary University Research
Initiative (MURI) was formed in 2001, led by
pincipl invtigto Gog Fih, ol
physicist at the Space Sciences Laboratory,
and several of his colleages also at UC
Bkly. Fom 2001 to 2006, Fih goup
ply th l ol in cooint ffotby nin ch intitution co th US
to invtigt th mchnim of mgntic
eruptions on the Sun and their effects on our
ol ytm t lg.
To understand the research at MURI,
we must first understand a bit about the
structure of our Sun. Imagine traveling from
th Sun co ll th wy to th outmot
layer of the Sun, the solar corona. To do
so, you would need to pass through three
distinct regions. You would start in the
deep interior surrounding the core, where
the energy generated by nuclear reactions
is transported by little packets of light
called photons. Next you would reach the
solar convection zone, a turbulent layer thatpn th out 30 pcnt o o of th Sun,
where energy is transported through rolling
convctiv motion, much lik in boiling
pot of water. Finally, you would travel out
though th ufc of th Sun t th top of
the convection zone, where the density of the
plm i low nough fo photon to cp
pt th coon n into pc.
While the core is extremely hot at 27
million degrees Fahrenheit, the tempera-
tu gully cool you tvl outw.
At the surface of the Sun, the temperatureis a relatively cool 9980 degrees. However,
as you move beyond the surface and into
the solar atmosphere, something strange
happensthe temperature suddenly rises
millions of degrees. Physicists generally
attribute this dramatic temperature increase
c u r r e n t b r i e f s
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Spring 2011 7Berkeley Science Review
to incorporate magnetogramsmaps of the
surface magnetic field observed by NASA
satellitesdirectly into a computational
model that includes the coronal magnetic
fil. Thi nbl nw pigm in ol
phyic: much lik imultion u fo t-
restrial weather forecasting, it is now feasibleto use previous observations of the evolving
magnetic field at the surface to predict its
futu tt.
Th UC Bkly-l MURI ffot h
deepened and extended computational
cpbiliti n llow litic moling
of how solar magnetic fields emerge and
evolve. Modeling how CMEs and other
eruptions are launched, however, remains
an ongoing challenge. The mechanisms that
trigger and drive these eruptions are the least
untoo pct of pc wth, yFisher. As yet, no one has demonstrated the
ability to use a physics-based solar model
that incorporates observed data to make
a deterministic prediction of a CME. To
t, ll CME foct ly upon ttiticl
ocition btwn how popti of th
solar surface have related to the occurrence of
CMEs in past data. All that can be said today
is that if the Suns surface looks a certain
way, we can guess that it might produce a
CME oon, with th optiv wo bing
might n oon.
to th ynmic mgntic fil tht th
it wy though th convctiv intio n
fill th coon.
The UC Berkeley teams primary goal has
been to develop and use advanced numerical
models to understand the physics behind
this dramatic temperature change and the
tigg mchnim fo uptiv vnt lik
flares and CMEs. These numerical tools
will hopefully be used to understand andpict th potntilly tuctiv gomg-
netic storms that result from solar eruptions,
providing a means to forecast space weather.
Unfotuntly, th lg vition in phyi-
cal conditions between the solar interior and
its outer atmosphere make such models
incredibly difficult to develop. The plasma of
the solar convection zone (between the core
and the surface) is dense, opaque, and turbu-
lent, whereas the solar corona is rarif ied and
transparent, with its structure and evolution
omint by it mgntic fil. Althoughch omin my b ptly untoo
quite well, a quantitative understanding
of th globl mgntic bhvio of th Sun
poses a formidable challenge, says William
Abbett, a MURI researcher at UC Berkeleys
Spc Scinc Lb.
To efficiently model and predict
the behavior of dynamic and electri-
cally charged fluids, physicists often use
a set of conservation equations called
Magneto-Hydro-Dynamic equations, or
MHD. Abbtt vlop pciliz cocalled RADMHD (RADiative MHD) that
i ign to imultnouly imult th
transition region between the cool dense
sub-surface layers and the hot rarified
coonth vy gion tht my hol th
key to a better understanding of coronal
hting n mgntic uption.
RADMHD has enough physics incor-
pot into th co to b bl to imult
th gnul convctiv pttn obv t
th Sun photoph, y Abbtt. A ky
strength of the RADMHD model is its ability
The UC Berkeley group is conducting
ongoing tui of p-CME coonl volu-
tion. On of th cunt objctiv of thi
research is a better understanding of how
magnetic flux systems emerge across the
solar surface, a process that some researchers
contend is primarily responsible for CMEinitition.
The Great Magnetic Storm in September
1859, known th Cington vnt, i till
the strongest magnetic storm on record.
For several days, it produced spectacular
uol iply tht w n t ltitu
low Hwii, n it vly iupt
telegraph communications in Europe and
Noth Amic. Toy, th ffct woul b
f mo vtting, ffcting pc-b
communiction, conninc, GPS, n
millions of users dependent on the powergrid. Is a similar magnetic storm in our
future? The MURI team cant say for sure,
even using their sophisticated RADMHD
co. In th ly month of 2011, th Sun
unexpectedly kicked up a series of unusually
intense X-ray flashes. Despite continuing
pog in ol phyic, w till hv lot
to ln bout ou cntl t.
Alireza Moharrer is an employee of the solar
power company Flagsol in Oakland, CA.NAsA
While the Earths magnetosphere protects it from most forms of solar wind, large magnetic surges in the outer
layer of the Sun, called coronal mass ejections or CMEs, can occasionally penetrate the Earths defenses .
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8 Berkeley Science Review Spring 2011
Whats theantimatter?Probing the origins of theuniverse with antihydrogen
For many, the word antimatter elicits
images of the Starship Enterprise ripping
though pc ft thn th p of l ight,
or canisters of tiny glowing balls threatening
to oblitt Vticn City. Scintific inccu-
ci in popul cultu i, th popct
of isolating antimatter, which annihilates
in but of light upon contct with mtt,
has eluded physicists for decades. And yet,
thi i jut wht goup of cintit wok-
ing at CERN, the European Organizationfor Nuclear Research, recently succeeded
in doing. Several months ago, the interna-
tional ALPHA (Antihydrogen Laser PHysics
Apparatus) collaboration, which includes
many researchers from UC Berkeley and
Lawrence Berkeley National Laboratory,
managed to create and, more importantly,
capture 38 antihydrogen atoms for about
one sixth of a secondan eternity in the
world of subatomic particles. This excit-
ing breakthrough will allow physicists to
study matters counterpart in detail and
will u ltimtly pn, n poibly fun-
mntlly chng, ou untning of th
origins of the universe. The first question
at hand: why is our universe made almost
ntily of mtt n not ntimtt?
A particle of matter and its antimattercomplement have the same mass but opposite
charges. While hydrogen is composed of a
proton and an electron, an antihydrogen atom
conit of n ntipoton, th poton ng-
tively charged counterpart, and a positron,
th poitivly chg nlog of th lcton.
Though cintit t CERN hv bn ct-
ing ntihyogn tom fom poiton n
ntipoton fo vl y now, thy hv
not been able to contain them for a signif icant
period of time. The net neutral charge makesth nti-tom impoibl to confin with n
lctic fil, n it kintic ngy mk it
chllnging to contol with mgntic fil.
Joel Fajans, UC Berkeley physics pro-
fessor and one of the lead scientists of the
ALPHA collaboration, explains the experi-
ment starting with the process of creating
antihydrogen atoms: Its not actually that
hardyou essentially just need to throw
together a lot of positrons and low-energy
antiprotons, and eventually you get anti-
hydrogen atoms. Just like UC Berkeleys
own Bvton, wh ntipoton w fit
discovered in the 1950s, the CERN laboratory
ct ntipoton fo vity of cintific
xpimnt. Unlik th Bvton, CERN i
uniqu in it cpbility not only to pouc
these particles, which are byproducts of high-ngy pticl intction, but lo to low
them down. Once cooled to low energies, the
plasma of antiprotons is introduced to a cloud
of positrons, letting pairs of particles combine
to form bound systemsantihydrogen atoms.
Th l ifficulty li in tpping th
antihydrogen atom, which Fajans group can
do with remarkable finesse. The ALPHA trap
consists of a complex system of repulsive
mgnt tht tk vntg of ntihyo-
gens magnetic moment to suspend the atomin space. However, despite state-of-the-art
technology, this is a very weak magnetic trap.
Even the smallest residual energy above a
ctin thhol llow th tom to cp.
Fajans likens the magnetic trap to a tiny
little dimple on a sheet of paper and the
antihydrogen atom to a ball rolling around
inside the dimple. Because the dimple is very
shallow, the ball will only stick in it if its
rolling very, very slowly. Despite the chal-
lenges, the team was able to coax many atoms
of ntihyogn to ty put in tht impl.
Briefs Antihydrogen
Antiprotons were first discovered at Lawrence Berkeley National Labo ratorys Bevatron.
l
bl
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Spring 2011 9Berkeley Science Review
A of lt Novmb publiction in Nature,
the ALPHA team had managed to isolate
38 pticl of ntihyogn fo jut nough
time to be sure of the new anti-atoms identi-
ti. Thy ubquntly tun off th tp
to l th ntihyogn n obv thresulting annihilation event. Since then, the
numb of tpp ntihyogn tom h
increased significantly, as has the time spent
in th tpup to bout 30 minut! Mo
tim in th tp mn mo tim to tuy
th popti of th ntihyogn tom.
Ultimately, the success of the antihy-
drogen-trapping experiment could play a
crucial role in filling a gap in the fields of
particle physics and cosmology. Currently
pf thoi tt tht qul mount
of mtt n ntimtt houl hv bnct in th conition tht w pnt
in the infancy of our universe. However, the
amount of matter overwhelmingly outweighs
th mount of ntimtt w obv in ou
universe. Conceivably, there could be a
galaxy out there made entirely of antimat-
ter, says theoretical cosmologist Chung-Pei
M, pofo of tonomy t UC Bkly.
However, signs supporting the existence
of such an anti-galaxy have never been
obv.
Experimental study of antihydrogenmight tk u tp tow untning
wht hppn to ll th ntimtt uing
th bith of ou univ. Do ntihyogn
atoms interact with gravity differently
thn hyogn tom? Do thy hv iff-
ent atomic signatures? If not, this is just
a gee-whiz experiment, Fajans remarks.
However, if there is indeed a difference in
the properties and behavior of matter and
antimatter, both Ma and Fajans agree that
thi woul hv volutiony impliction
for how physicists think about the begin-nings of our universe. The general consensus
mong cintit i tht fining th iff-
ences seems highly unlikely, though the mere
poibility of uch pofoun icovy i
very exciting. We may never be able to power
spaceships with antimatter, but the search
fo nw to th myti of th univ
will nv un out of ful.
Denia Djokic is a graduate student in nuclear
engineering.
Hormonal hassleHow stress can hurt your sexdrive
Weve all been there. You come home after a
stressful day at work and find yourself barely
motivated enough to eat dinner. Despiteyour partners advances, being intimate is
th lt thing on you min. Thi poblm
is not unique to humans; the opposing
ction of t n x i n iu fc by
all species on our planet. It is a basic fact
of life that energy spent on reproduction
mut b blnc gint lf-uvivl, but
only in th lt tn y hv ch
pinpoint on of th homon cpbl of
turning off sex drive in response to external
to.
The discovery of a molecular linkbtwn t n x cm fom ch
studying the effects of stress on bird and
rat behavior. George Bentley, Associate
Professor of Integrative Biology at UC
Berkeley, showed that stressed animals have
elevated levels of gonadotropin-inhibitory
hormone (GnIH). GnIH prevents proper
sperm and egg development by blocking
th ction of gonotopin, wll-tui
class of hormones secreted from the pituitary
gln tht timult pm n gg mtu-
tion. The connection between GnIH andt vl th fit known mchnim
of how nvionmntl t (.g. pto,
storms, etc.) suppresses the reproductive
ytm of niml.
Researchers discovered GnIH ten years
ago while searching for new hormonal
gulto of niml bhvio, fining tht
it was capable of inhibiting the release ofreproductive hormones in quails. Their
study motivated Bentley to test the func-
tion of GnIH in pow, pci tht h
long served as a model for reproduction
research due to its complex mating behav-
ior. A link between quails and sparrows
would verify the evolutionary importance of
GnIH whil lo llowing u to invtigt
it ffct on mting bhvio, y Bntly.
By administering GnIH directly to the
brains of female sparrows, Bentley found
an immediate decrease in levels of lutein-izing hormonethe hormone responsible for
ovulation. Remarkably, he also saw a change
in behavior. Female sparrows normally find
the song of male sparrows irresistible, but
direct administration of GnIH decreased
th fquncy with which fml pow
solicited copulation. This marked the first
discovery of a hormone capable of negatively
gulting x homon n bhvio.
Given its ability to turn off sexual behav-
ior in animals, GnIH may be the long-sought
link between stress and sexual reproduction.Bentleys work with wi ld birds supports this
hypothi. W t bi whn w ctch
Briefs Stress and sex
l
uissilvA Research led by Professor George Bentley is uncovering the molecular links be tween stress and libido by obser ving
mating habits and biological changes in stressed-out sparrows. Mapping out these biological links is the first
step to understanding the effects of stress on the human libido.
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10 Berkeley Science Review Spring 2011
thm in cloth bg, xplin Bntly, n
once they are captured their GnIH levelsincrease dramatically. These findings
describe the first connection between stress
and sex drive: the release of stress hormones
activates neurons in the brain that secrete
GnIH, leading to widespread decreases in
reproductive potential and behavior. This
mk intuitiv n, y Bntly, bcu
if th i mjo tom, it woul b b
idea for to you lay eggs; they would probably
not uviv.
After his latest observations in birds,
Bentley began looking for a connectionbetween GnIH and stress in mammals. In
collaboration with Daniela Kaufer, Assistant
Professor of Integrative Biology, Bentleys lab
cutly t t with th hou immo-
bilizations. Initial experiments showed an
increase in GnIH levels accompanied by a
c in lutinizing homon n, th-
fore, in ovulation. Furthermore, rats that
experienced chronic stress, brought on by
immobilization for three hours a day over 14
days, had significantly higher levels of GnIH
and lower levels of luteinizing hormone than
rats that experienced acute stress. The ability
for chronic stress to elicit higher levels ofGnIH i th intting poibility tht
GnIH release may limit or turn off repro-
uctiv iv compltly, pning on th
xtnt of nvionmntl t.
Bentley has also been looking for GnIH
in other species. Comparison of GnIH DNA
sequences allowed him to discover GnIH-
lt homon in multitu of pci
uch hmt, hp, n vn humn.
On of th fit thing I i whn I tt
my lb t UC Bkly w to bgin looking
fo th pnc of GnIH in humn bin,says Bentley. His preliminary work has
shown that GnIH is indeed present. Even
though a functional link still needs to be
tblih, mny volutionily conv
gn btwn bi, ont, n humn
tend to retain the same function, so it is likely
tht GnIH ply ol in ngtivly gult-
ing humn xul bhvio.
Michael Cianfrocco is a graduate student in
biophysics.
Its a bird...its aplane...its a robot!
Machines that fly themselves
The big one has hit. After an earthquake,
remains of buildings lie in haphazard heapsof debris, forming elusive recesses inaccessi-
ble to even the most experienced rescue team.
A small group of flapping-winged robots
swoops in to locate otherwise hidden victims
trapped beneath the wreckage. Capable of
autonomous scouting, these mini-bots
would be equipped with surveillance, heat
sensors, and GPS, all elements that would
help identify the location of victims or struc-
tul hz in th vnt of n mgncy
lik th cnt thquk in Jpn. Whil
such technology is still a distant prospect,ccoing to Stn Bk, gut tunt
in Professor Ron Fearings
Biomimetics Millisystems lab at
UC Berkeley, it does moti-
vate the labs research
in the development
of flapping-winged
obot.
A logical starting
point for designing a f lying
obot might b to pt th
design of an airplane and min-ituiz it. Th woking compo-
nents of conventional airplanes
conit of tubin ngin n n
assortment of rudders, stabilizers, and
wing. Thi typ of igi-wing fl ight
provides stability (minimal turbulence)
n of mnufctuing, ftu which
hv m uch ytm xcllnt fo com-
mcil ppliction. Howv, thi kin of
flight is limited in its range of motion and has
not bn povn to wok in vy mll-cl,
insect-sized systems. For an autonomous,highly mnuvbl couting vic to b
feasible, a different kind of flight mechanism
i qui.
Taking their inspiration from nature,
Fearings lab has chosen to develop a flap-
ping-wing design for their mini-bot. Unlike
propeller-driven and rigid-winged flight,
flapping f light provides an incredible range
of il contol. Bif obvtion of bi
in flight or a darting dragonfly highlights its
quick, agile movements, hovering capabil-
ity, and maneuverability. Winged flight in
Briefs Stress and sex
GnIH
G
nIH
GnIH
GnIH
GnIH
GnIH
GnIH
GnIH
GnIH
GnIH
GnIH
GnIH
GnIH
GnIH
GnIH
GnIH
GnIH
GnIH
GnIH
GnIH
GnIH
GnIH
GnIH
GnIH
GnIH
GnIH
GnIH
GnIH
GnIH
GnIH
EmotionalPhysical
Environmental
Mental
Nutritional
Social
Work
sex drive
f
roml
eft:kAthryNbAldwiN;stANbAek
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nature is resilient in all kinds of environ-
ments and is known to work for creatures
miv goln gl n mll
a gnat. If researchers better understood this
type of f light, they could use this knowledge
to engineer small systems that mimic itsfficint n ynmic motion.
Over the past few years, the Biomimetics
lab has been developing an autonomous
bird-like robot, known as iBird. As a test
model, Baek and fellow graduate student
Fernando Bermudez have taken the body of a
store-bought, radio-controlled glider (which
thyv ubb th onithopt) n moi-
fi it. Th bin of th obot, n onbo
microcontroller, is equipped with an antenna
for receiving signals and various motion sen-
sors to monitor the ornithopters movement.In o to mk iBi fully utonomou, it
must be a self-contained entity capable of
interacting with its surroundings without
communicating with a human controller,
by no mn n y tk.
In the past few years Baek and Bermudez
have successfully implemented two impor-
tnt contol lmnt: opticl flow n lti-
tu gultion. In obotic, opticl flow i
u fo colliion n obtcl voinc.
In concert with other sensors, it can
lo b u fo vlocity timtion.Optical flow measures how fast a
light o k pot mov co
an image, information that
cn b u to intify th
distance between the
robot and an object,
and whether or
not th objct i in th obot pth. To
opticl flow to thi vic, th tm u
a high-resolution cell-phone camera in
tandem with a commercially available visual
processing chip. For altitude control, Baek
u n inf no fom th NintnoWii mount on iBi n pnl of ngl
light emitting diodes (LEDs) for monitoring
and controlling the relative altitude of the
bi bot. Th LED iply t vl ft
away from the bot on a shelf or table. The
light fom th LED ch th Wii no
from several directions and thus, within a
ctin fil of viw, iBi hight ltiv
to the panel can be determined. The bot also
i o fll pning on th light input it
observes. Baek and Bermudez hope to extend
this control and have the bot follow a movingtarget, and perhaps have a set of bots interact
n follow on noth jut lik bi flying
in flock.
In the near future the group plans to
improve upon the current prototype by
incorporating additional controls such as
plnning contol n Popotionl Intgl
Derivative (PID). In planning control,
restrictions are placed on the bots movement
to maintain its equilibrium. For example,
th thn tking hp 90-g tun,
which might disrupt the ornithopters bal-nc, with goo plnning contol th obot
would take the turn gradually. The PID
system monitors deviations in the velocity
n ccltion of th obot (o ny oth
mubl pmt) n jut th
pmt vi fbck loop.
Although much has been accomplished
since the project started about four years ago,
the team stil l faces many challenges. Winged
flight i itlf pooly tui ytm; com-
puter simulations take days to run and f light
dynamics become very complicated because
material flexibility, weight, wing size andmny oth pmt mut b tkn into
account. The team has used experimental
t fom tt un to cicumvnt thi lt
poblm.
Once the software components for an
autonomous robot have been developed and
thoroughly tested, the next step will be to
miniaturize the system. From observing
nature, we know for certain that flapping-
winged flight can be miniaturized, Baek
says. The next step for smaller-scale
flapping-winged robots will be to find asmall battery source that can supply enough
pow to iv th ytm, long with wy
to design a lighter control board that will
perform fully autonomous f lights without
mot contol ignl.
In the future, the majority of the
mechanical aspects of iBird will be developed
by Sunil K. Agwl ch goup, col-
laborating team at the University of Delaware.
Th Bkly lb pimy focu i to ct
software algorithms that will mimic intel-
lignt bhvio in thi wing-flight obot.With the addition of more controls, Baek
is hopeful that iBird may one day soar on
it own.
Claudia Avalos is a graduate student in
chemistry.
Briefs Bird-bots
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12 Berkeley Science Review Spring 2011
Smart circuitsMaking electronics thatremember
Electrical engineering is on the cusp of a
breakthroughone that will allow engineers
to create circuits that drastically increasethe speed of processing, use far less power
than modern computers, and even mimic
th kin of computtion ci out by th
humn bin. Thi hift com in th fom
of the memristor, a long-theorized but only
recently constructed electrical component
that stores information about its past activity
and uses this information to influence its
behavior. First theorized nearly 40 years ago,
and finally built by Hewlett-Packard Labs
in 2008, it pomi to fin th biliti
n ppliction of comput of th futu.While memristors have only recently
bn contuct, thy hv xit in tho-
retical electronics for many years. Leon Chua,
longtning mmb of th Dptmnt
of Electrical Engineering and Computer
Sciences at UC Berkeley, laid out the original
theory in 1971. In his paper, Chua addressed
hol tht xit in ou knowlg of lc-
ticl ngining.
Th wol of lctonic i lgly built
around devices that carry out interactions
between the basic variables in any circuit:
charge, resistance, voltage, and flux. For
example, a capacitor creates a voltage by
maintaining an imbalance of electrons (or
chg) on ith i of gp. At th tim
of th thoy publiction, th w clexplanation for how a real-world device
could connect each combination of these
lmnt but on: chg n flux.
Chua theorized a new circuit element
to carry out the missing interaction. This
element would behave very similarly to a
resistor, but with one key difference: the
amount that it impeded the f low of electricity
would depend on the current that had already
passed through. In essence, this electrical
lmnt woul hv mmoy, combining
infomtion bout th pt with it input inthe present. For this reason, Chua dubbed
thi nw lmnt th mmito.
Though it made a splash in theoreti-
cl lctonic, it woul b nly 40 y
until the memristor would be realized in the
laboratory. Up to that point, Chuas depiction
of the properties of memristors had been
likn to th luiv Higg boon of tho-
retical physics: a particle that exists in theory
but has not yet been observed. Then, in 2008,
HP Lb nnounc tht thy h ct
nano-scale circuit that showed exactly the
same properties that Chua had theorized.
Mmito w l.
Although memristors have yet to
be successfully integrated into standard
electronics, the ability to engineer circuitswith mmito i impoving pily, n
hybrid memristor/traditional computers are
xpct to mk thi fit ppnc in
conum tchnology in th nxt fw y.
You nxt comput coul hv mmito
tht llow fo ft booting n pocing.
These early successes bode well for a para-
digm shift in the future of electronics. While
most modern computers perform calcula-
tions using dynamic random access memory
(DRAM) that must be wiped clean every time
a computer loses power, a new memristor-equipped computer could remember the
state from when it was last turned off and
boot up nly intntnouly.
Memristors could also decrease comput-
ers power consumption, which has increased
exponentially as demands on processors
continue to rise. Currently, this power
conumption po ignificnt chllng
to increasing the complexity and power of
processing chips. Memristors, however, con-
um ltivly littl pow bcu toing
mmoy within mll unit, th thn ina separate system, allows designers to use
fewer and shorter wires, and thus less power.
Mmito ytm bing t clo to com-
putation, much as biological systems do,
explains Massimiliano Versace, a researcher
at Boston University who is using memristors
to study, and possibly create, models that are
inpi by humn cognition.
Th potntil to ct highly intcon-
nct ytm tht ily imil to th
wy ou own bin tuctu i on of
th mot xciting potntil ppliction fommito. Fo mny y, cintit hv
tried to model human cognition, but have
often fallen short due to the limitations of
our current hardware. Such systems are built
with specific locations for computations (cen-
tl pocing unit, o CPU), hot-tm
mmoy (ynmic nom-cc mmoy,
or DRAM), and long-term memory (the hard
Briefs Memristors
An image of an ar ray of memristors formed at the
intersection of crossed microscopic wires. Each is
approximately 150 atoms wide. hplAbs
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n 1972, geneticist Susumu Ohno
coined the term junk DNA to
describe every component of the
human genome that was not a gene.
Suspicious of the assumption that
all three billion base pairs of human DNAwere functionally important, Ohno wrote,
Tiumph wll filu of ntu pt
xpimnt pp to b contin in ou
genome. Nearly a decade later, Francis Crick
and Leslie Orgel published a review in Nature
entitled Selfish DNA: the ultimate parasite,
arguing that most DNA in higher organisms
w, imilly, littl btt thn junk.
For many years, the idea that the genome
was divided cleanly into two categories
hot ttch of gn intp mong
long pn of junkw wily ccptview. But by the early 1990s, the concept had
bgun to gow tl. Gnticit w gu-
ally uncovering more and more functionally
ignificnt ol within th junk gion,
n th vy finition of gn itlf w
beginning to change. Nevertheless, when
th full qunc of th humn gnom w
finally published in 2004, many people were
hock to icov jut how fw gn ou
DNA actually contains. Representing only
two percent of the entire genome, genes were
vast ly outnumbered by myster ious non-coding regions. But if this dark genome
really wasnt junk, what could it al l be doing?
A manifold blueprint
DNA i m up of fou if fnt molcul
called nucleotides, paired and bound together
to form the two anti-paral lel twisting threads
of th oubl hlix. Som gmnt of DNA
are known as genes, meaning that theirnucleotides will be transcribed into a slightly
iffnt chmicl fom cl l RNA. A p-
cific type of this RNAcalled messenger
RNA, or mRNAwill then leave the nucleus
to serve as a template for synthesis of the
protein building blocks that carry out our
cellular processes. Proteins not only make up
th tuctul fmwok of ou cll, thy
also catalyze most of the chemical reactions
tht mk cll wok.
Yet all cells, from kidney cells to neurons
to muscle cells, possess exactly the same copyof DNA. In it ntity, DNA xit only
template from which an immense number of
readouts can occur; not all genes are expressed
t ll tim in ll cll, n it i pcily thi
capacity for different combinations of expres-
ion tht llow fo th tonihing ivity
of ou cllul poc. Gnticit till
unclear exactly how these highly ordered pat-
terns of gene expression are achieved. The
nw my li in th k gnom.
From base to functionTh chitct of th moENCODE pojct
ought to chip wy t thi qution by fit
mbling mp. By nnotting th func-
tion of vy b of DNA in th two mol
ognim, thy hop to gin om inight
into how transcription is regulated across cell
typ n thoughout vlopmnt.
They analyzed function along two
bo t of fcto. Th fit t, f
to as functional elements, include small
potin tht gult tnciption, wll
as non-coding RNAs (ncRNAs) that helpto gult gn xpion ft tncip-
tion but before protein synthesis. The second
set, known as epigenetic elements, are not
contained in the sequence of DNA itself, but
include chemical marks on the surface of
DNA that physically inf luence what regions
of th gnom ilnt o ctiv. Ov 50
participating labs around the world analyzed
specific types of functional or epigenetic
elements in one of the two model organisms
to assemble a topographical map of function
long th lin DNA qunc.
When you first think about genetics
15-20 years ago, the goal was simply to
untn th coth co it lt
to genes, gene expression, and the produc-
tion of proteins, says Gary Karpen, a senior
tff cintit in th Lif Scinc Diviionof Lawrence Berkeley National Laboratory
(LBL). But then it became clear that the
co w imply not nough. Kpn n
tm of ov 150 oth cintit hv jut
completed an ambitious project whose aims
were, according to Karpen, the next level up
fom tight cot th lvl of mpping
function in the dark genome. What is emerg-
ing i f btt i of th impotnc of
thi lgly unxplo gntic lncp,
picture of DNA as a dynamic template for life.
The birth of modENCODE
The project, called the model organism
Encyclopedia of DNA Elements (modEN-
CODE), was born out of a sister initiative
launched in 2003 called ENCODE, which
im to ctlog th complt pt lit of
the entire human genome. The pilot phase of
ENCODE cnt on nnotting only on
percent of human DNA, but the complex-
ity of th humn gnom n th limit of
tchnology t th tim ncitt light
hift in focu.Thus, in 2007 the National Human
Genome Research Institute (NHGRI)
lunch moENCODE plll ffot
involving two simpler subjects: the round-
wom Caenorhabditis elegans n th fuit
f lyDrosophila melanogaster. Th fou-y,
$57 million project hoped to identify, if
possible, the functional role of every
base in the worm and fruit f ly genomes.
These two model organisms represent
far better understood genetic systems
than the human genome and, at 100and 180 million base pairs each, far
more feasible approaches to the
genome-wide analysis NHGRI
im to chiv. Th hop w
that ultimately modENCODE
could serve as an extended
pilot for the entire human
ENCODE project, helping us
better understand how it is that
complex, three-dimensional
organisms arise out of linear
tn of DNA.
features Dark genome
I
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Spring 2011 17Berkeley Science Review
The transcriptome
We wanted to crack the code to discover
the rules required to read a genomeany
gnom, y Sun Clnik, h of th
Department of Genome Dynamics at LBL
who, along with Karpen, was one of the
senior principal investigators for modEN-
CODE. Her lab was on the Drosophila team
and was responsible for mapping out the
nti tnciptomll of th qunc
of DNA tht tncib into RNA.Counting both coding and non-coding
RNA, th tnciptom compi bout
60 percent of the fly genome. In order to
screen such vast amounts of RNA with
single-base resolution, Celnikers group
used a high-throughput technique known
RNA-q. Invtigto iolt th mo
than 25 million scattered fragments of RNA
that have been transcribed from DNA. After
mking om chmicl moifiction tht
allow sequencing to occur, they convert
the RNA back to DNA through a process
called reverse transcription, giving them the
coing DNA, o cDNA, fo th oiginl t
of RNA fgmnt. Thy thn qunc th
cDNA and align it with the original genome
qunc to mp th tnciptom.
Clnik goup gnt lmot ix
thousand-fold coverage of the previously
annotated fly transcriptome. Combing
through their RNA-seq data, they identi-
fi nly two thoun nw tncib
regions that had been missed in previousannotations. These new regions include
sequences that encode small proteins, as
well as small non-coding RNAs that par-
ticipate in the regulatory machinery that
help control gene expression and protein
production. In perhaps their highest-impact
finding, Celnikers group identified over
22,000 new splice junctionsareas where,
after transcription, distinct chunks of
tncipt cn b cut out, llowing fo if-
fnt combintion of mRNA. Altntiv
splicing thus allows a single gene to code
features Dark genome
fo vl if fnt potin, b on th
different possible patterns of cutting and
pting.
The discovery of the vast number of
previously unidentified splice junctions
and new transcripts gives us a far better idea
of the sheer quantity of potential protein
products in each cell. Insight into an addi-
tional layer function, however, is provided
by th intifiction of th nw non-coing
RNAs, many of which are involved in splicingevents, promoting or repressing transcrip-
tion, o ilncing mRNA to finly contol
lvl of potin ynthi. Th ovlpping
output of these two mechanismsvariety
of combintion within tncipt n n
intricate regulatory machineryis crucial
to untning ou gnom iffntil
woking fom cll to cll.
Illutting thi, Clnik goup thn
ci out compion co 27 itinct
developmental stages as well as between
th x. Inttingly, thy foun tht th
In alternative splicing, a single gene can be read in multiple ways to produce different proteins. After transcription occurs (step 1),
distinct segments of the RNA called introns (gray) are removed by cuts made on both sides at locations called splice junctions. The
remaining RNA (colored) can then be reconnected to form different strands of mRNA (step 2). The different mRNAs will then serve
as templates for the s ynthesis of different proteins (step 3).
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18 Berkeley Science Review Spring 2011
To fit inside each individual cell, DNA must be condensed and packaged into fibers called
chromatin. The double-stranded helical DNA first wraps around clusters of proteins called
histones. The histones are arranged along the DNA like beads on a string, allowing the
histone-DNA spools to coil, fold, and loop around themselves. The final product is the
tightly packed fiber of chromatin, organized into distinct sets of chromosomes.
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Spring 2011 19Berkeley Science Review
number of expressed genes increases from
oun 7,000 in mbyonic fli to oun
12,000 in adults. They also analyzed changes
in expression patterns of specific genes across
vlopmnt, fining gn tht highly
upregulated in the larval developmentalstages and then essentially shut off as the
fly mtu. Btwn th x, thy not
tht ult ml xp oun 3,000 mo
genes than their female counterparts. Thefunctions of all of these genes are not yet
known, but they are al l clearly implicated in
developmentboth across time and between
sexes. Celniker hopes that her groups identi-
fication of the genes will spark more targeted
ch in th Drosophila community.
For me, says Celniker, the project will
not be over until I know exactly how a single
cll with it ingl copy of DNA tun into
complx ognim lik th fly. W not
there yet, but were certainly assembling the
builing block.
The chromatin landscape
With 100 and 180 million base pairs even
in ognim impl th wom n
th fuit fly, ch copy of DNA i imply too
long to exist as a linear molecule in a tiny cell.
Int, it i conn n pckg into
chomoom pith wom h ix n
th fuit fly h fou, whil humn hv 23.
Chromosomes are made up of chromatin,
which consists of DNA wrapped around clus-
ters of tiny proteins called histones, arrangedalong the DNA like beads on a str ing. These
hiton-DNA pool thn upcoil oun
themselves in meandering loops and folds,
finally forming the t ightly-packed structure
of chomtin.
Kpn n hi lb t LBL tuy wht
is called the chromatin landscape of the
fruit f lythe hundreds of chemical tags that
can be added to histones to ultimately affect
levels of transcription. The modifications
thn cogniz by th cllul mchin-
ery that respond to these chemical signals,
resulting in silencing or activation of the
DNA in th tgg gion of chomtin.
Histone modifications are one of several
types of epigenetic mechanisms that influ-
nc gn xpion. Thy not nco
within th gnom; th, thy impct threadout of DNA through changes to the pro-
tein components of chromatin. These epigen-
tic chng lo hitbl, mning th
modifications are passed along through celliviion n cn l to uniqu igntu
mongt iffnt cll typ.
Mot of th tim, popl hv tui
these histone modifications in isolation,
y Kpn. But wht w w intt
in i how thy wok in combintion. Uing
a method called chromatin immunopre-
cipitation (ChIP) and high-throughput
sequencing, Karpen and his group were
able to identify chromatin marks associ-
t with viou gion of th fly gnom.
By looking t iffnt combintion of 18specific chromatin marks, they delineated
about 30 distinct chromatin states correlated
with the position of genes and their levels
of xpion. Th tt inclu highly
predictable associations with transcrip-
tion tt it, gn lngth, ilnt o ctiv
regions, and even gene function. Theres
an issue here with cause and effect, Karpen
y. It not jut th typ of moifiction
thats important, but where the modification
i, which hiton, which mino ci in tht
hiton, wht cogniz tht moifiction,wht oth potin bought inth
lot of complxity.
Karpen stresses that this is just the
beginning of this type of broader analysis
of chromatin marks; although they
thoroughly characterized 18
histone modifications, hun-
min. Rgl,
Karpens work adds
another topographical
layer to the genomic
landscape. While
features Dark genome
functional elements control gene expression
t th lvl of DNA n RNA, tnciption
and protein synthesis, epigenetic elements
allow for yet another route of cell diver-
genceone that occurs above the level of
DNA sequence. This is really the level ofdynamic genomics, Karpen says. I have to
y, I jut fin th fct tht w know o littl
incibly xciting.
From map to model
Once the individual research groups had
all assembled their final data, Drosophila
moENCODE h ov 700 tt pofil-
ing tncipt, hiton moifiction, n
replication programs. Karpen, Celniker, and
th t of th Drosophila tm thn ubmit-
ted their finished datasets to Manolis Kellis,head of the Computational Biology Group at
Massachusetts Institute of Technology. Kellis
headed the modENCODE Data Analysis
Cnt, which took ll of th finih t
n intgt it into cohnt toy, ct-
ing th pictiv n comptiv gnom-
ics models that the consortium hopes will
eventually help shed light on parallels in the
humn gnom.
The biggest question we asked ourselves
was, how do we go beyond simple annota-
tion? How do we compare all these datas-ets together to reveal new insights? says
Klli. To o o, Klli n hi goup t MIT
attempted to reconstruct the full regulatory
ntwok of th fly fom th pool tt.
To assess the completeness of their
contuct mol, Klli Dt Anlyi
Cnt ttmpt to pict
gene expression
We can only assume that the rules are there and
keep looking. But the reproducibility of biology
tells us that these rules must exist.-Manolis Kellis, modENCODE computational biologist
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20 Berkeley Science Review Spring 2011
levels based solely on the expression levels of
thi gulto. Looking co numou
vlopmntl tg n cll lin, Klli
group was able to successfully predict over 60
percent of gene expression patterns in about
qut of th cll lin tui.
These are only very preliminary models,
Kellis says, and predicting the expression
patterns of an entire genome remains
an enormously complex problem. For
modENCODEs first round of predictivemoling, fo xmpl, th goup w only
able to incorporate a certain subset of pre-
transcriptional functional elements whose
targets are already well-established. As more
and more of the targets of the newly mapped
gion chctiz, Klli n oth
in the computational field wil l be able to cast
wi nt to t out th unlying logic
of gnomic. W cn only um tht th
rules are there and keep looking, says Kellis.
But the reproducibility of biology tells us that
th ul mut xit.
The future of ENCODE
The original draft of the human ENCODE
stated that the project would proceed in three
stages: a pilot phase, a technology develop-
ment phase, and a production phase. Now
that modENCODE is complete and the
mthoologi finlly tt n fin,
all that remains for ENCODE is the mas-
iv pouction ph. Th bn lot of
thinking about how to go about systematically
untning th humn gnom, n itout of those conversations that modENCODE
mg, y Klli. Th tk i no l g-
gntun, but with th tchnology n fm-
work finally in place, a completed human
ENCODE my only b fw y wy.
With the modENCODE papers now
publih, mo thn 80 pcnt of th fuit
fly genome is annotated and fully available to
th publicup fom bout 25 pcnt bfo
the project began. Yet though the consortium
h mbl n impivly hug tt,
we are still unable to trace exactly how a single
features Dark genome
o
pposite:mArekJAkubowski
Histone modifications are one of many cellular mechanisms that work to control gene
expression. Possessing long amino acid tails (yellow), histones can be tagged with chemical
modifications (red). These tags are then recognized by other cellular machinery that can
work to silence or activate the DNA in that region. Histone modifications are a type of
epigenetic mechanism, meaning they are heritable but not encoded directly in the genome.
cell with a single copy of DNA becomes a
complex living and breathing organism. The
Drosophila and C. elegans genomes have been
mapped, but its really only the faint outlines
of function that have emergedwe do not
yt know th intict mchnim by which
each of the elements work, let alone their very
pcific tgt. Th moENCODE pojct
w lly jut intt in poviing tt-
ing mapthe equivalent of the first explorers
coming to the New World, says Karpen. Wen lg-cl pojct lik thi to povi
the kind of foundational knowledge that
llow th mo intict mchnim to b
worked out from there. A complete under-
tning of lif gntic computtion my
b f off, but w now hv th fit mp to
gui u. Th k gnom i gtting light
n light.
Azeen Ghorayshi is a research technician in
molecular and cellular biology.
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h an anby Jacqueline Chretien
Baby lab
n tht bn invtigt, bbi n chiln mkblypt t lning. But whil thy my b xcllnt t figuing outthe world around them, its still unclear exactly how much theyknow, n whn, n wht mchnim in plc to llow thipi lning.
Armed with colored ping pong balls , light-up lollipops, stuf fedanimals, and invented words, researchers in the Xu lab are making
strides toward answering these questions. The answers they f ind mayhave applications in fields from parenting to computer programming.
My nine-month-old daughter, Ellie, is a statistics genius.Thi my oun lik typicl nw mom bgging, but
it not; it cintific fct. Accoing to ch fomProfessor Fei Xus Infant Cognition and Language
Lb in th Dptmnt of Pychology t UC Bkly, th vgsix-month-old is pretty good at making basic estimates of probability,
and by the time they learn to walkaround a year oldmost babies
xpt. Chiln lo mt of lngug cquiition, pt-tn cognition, n inuctiv oning. In fct, in lmot vy
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22 Berkeley Science Review Spring 2011
block, th lot of logicl poibiliti
to wht th wo coul b fing to. It
could be referring to the color yellow, it could
b fing to omthing h, it coul b
fing to omthing on my hn.
But ki ont un though ll of th
possibilities every time they learn a new word.Instead, they have a number of biases that
hlp thm now in on th ight finition
fairly quickly. For example, children tend to
assume that a word refers to an entire object,
rather than just part of itcar describes
the whole vehicle, not just its hood. Similarly,
they assume that labels apply to the shape of
the object, rather than another character-
istic, like color or texture. This is a useful
assumption, because objects are likely to
have a stereotypical shape (a ball is usually
bll-hp, cup i uully cup-hp)
Whats in a name?
Its the oldest debate in developmentalresearch: do we learn to learn, or are we
simply biologically programmed to soak
up infomtion fom ou uouning n
xpinc? Th obviou nw, of cou,
is that its probably a little bit of both, but the
precise location of the boundary between
nature and nurture is a matter of intense
bt.
Postdoctoral researcher Sylvia Yuan
is investigating this boundary by studying
word learning in toddlers. Previous research
has suggested that by the age of two or so,chiln hv numb of cognitiv bi
tht hlp thm olv th nly impoibl
logic problem of what words mean. Even
if we explicitly label something, like, this
is a Lego, Yuan says, holding up a yellow
daxes, while animals with a different set
of mk on th two ppng might bblickt. H, th uul bi nt hlp-
ful, o chiln hv to ln not only wht
each animal is called (the hypothesis), but at
th m tim figu out wi nw ul
tht govn how th niml nm
(th ovhypothi).
By manipulating this basic experimental
setup, researchers can ask what variables
affect how children form overhypotheses.
On ky fining h bn tht th numb
of categories presented seems to be more
important than the number of examples percategory. Preschoolers shown eight animals
mo ily bl to clify thm if th
are four categories with two animals each
(two daxes, two blickets, two faps, two zoogs)
than if there are two categories with four
animals each (four daxes and four blick-
ets). This suggests that each new category
a child sees either strengthens or changes
her overhypothesis about how categories
fin in gnl, inicting tht it
ynmic poc.
Yuan plans to use these initial studies asa launching point to investigate how other
factors, like adding noise by varying the
iz o hp of th itm, o intoucing
exceptions to the rules, affect overhypothesis
formation. Increasing the number of non-
informative marks, for example, could go
either wayit might help children focus in on
the actually useful information more quickly,
o it might jut confu thm. W tying
to figu out wht th nvionmntl input
tht mk it i o h fo thm to
chiv n ovhypothi, Yun y.
but my not lwy com in th m colo
o iz.Th bi hv long bn thought to
b innt, inc thy i o ly in vl-
opment and are so universal. Intriguingly,
though, children seem to weigh information
iffntly pning on th typ of objct
thats being defined (color, for example, is
more important when learning the names
of foo, whil txtu bcom impotnt
when learning the names of animals), sug-
gting tht xpinc might ply ol in
bi fomtion.
This process of bias-building is referredto ovhypothi fomtion. A thy
learning about each word, Yuan explains,
thy might b tting in thi h: i it th
txtu, i it th colo, i it th hp? An
whn thy noth xmpl, thy might
be thinking, okay, it doesnt seem like its the
texture, it seems like its more the shape. As
chiln fom hypothi bout wht ch
objct i cll, thy lo foming mo
abstract rule, or overhypothesis, that defines
how objct nm ign in gnl.
Yun n oth in th lb tying todetermine what factors affect overhypothesis
fomtion whn chiln cquiing nw
vocabulary. Instead of examining established
biases, like shape, the lab introduces artificial
categories so they can study the overhy-
pothesis formation process as it happens.
In one typical experiment, preschoolers must
figu out tht mking on th til n lft
foot of othwi inticl tuff niml
determine their identityfor example, ones
with a question mark on the tail and an
xclmtion point on th lft foot might b
features Baby lab
Months 6 9 12 24 36 48 60
Infant Toddler Child
ping-pong ball study
infant overhypothesis
lollipop study language overhypothesis
shape bias studies
imitate sounds rst words full sentences storytelling
crawlingrolling over running
walking
rst smiles peek-a-boo recognizes reection imaginative play
m
ArekJAkubowski
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Spring 2011 23Berkeley Science Review
Behind door number three...
Thi ot of mt mchnim tht llow
chiln to w up bo, ognizing pin-
cipl b on mll numb of xmpl
i cucil fo lning. Without n fficint
way to generalize the knowledge gained fromone experience and apply it to another, it
would simply take too long for kids to figure
out how the world works. (And as anyone
who has ever watched a child repeatedly test
gravity with the food items on her high chair
tray wil l tell you, it takes long enough as it is.)
But until recently, it hasnt been clear whether
overhypothesis formation is limited to word
lning, o whn thi kill fit i.
Our working hypothesis is that there is
a set of learning mechanisms in children that
support rapid learning, says principal inves-tigator Fei Xu. She and others have predicted
that even babies less than one year old might
be able to form overhypotheses, but probing
infant psychology can be difficult. Simply
working with babies can be a challenge in and
of itself. After all, there arent many fields
in which pp outinly inclu lin lik,
An itionl fou ubjct w tt but
excluded due to fussiness. Entertainingly,
researchers report that fussiness isnt as
much of a problem as bodily functions.
Stephanie Denison, a graduate student inthe lab, puts it delicately: Occasionally they
get distracted by... digestion during the trial.
Yuan elaborates, We would have observ-
wit own, fo xmpl, fc i ll
n quinty... th ki ot of top looking
at whats going on on the stage and in the
trial. Distractability can also be problematic.
One little one just pulled off her socks in the
mil of it. Th foot flying ov th,
a foot f lying over here, lab manager Christie
Reed recounts. And the occasional baby will
fll lp uing tuy, too.Its also tough to find experimental
methodologies that can truly illuminate
infant cognition. Smart as infants are, it
is hard to work with them, since they do
not yt tlk o follow intuction, Xu y.
Rch cnt jut k vy young bbi
wht thy thinkingthy hv to figu
it out in om oth wy. W oftn cpitl-
ize on the fact that infants, just like older
chiln n ult, vy cuiou, y
Xu. Thy py mo ttntion to thing tht
nw, intting, n unxpct. Thi
i u to ch vntg
in the classic looking time/viola-
tion of xpcttion mu,
well-established test for deter-
mining wht bbi bl to
predict. Because babies spend long tim looking t thing
that are novel or surprising,
an infants looking behavior
cn b mu to povi
mtic of whth h fin n
vnt xpct o unxpct.
Measuring looking time was crucial for
the Xu labs studies of overhypothesis forma-
tion in infants (as opposed to the toddlers in
the object naming study). In these experi-
ments, nine-month-olds watched while a
researcher removed objects from variousboxes. The first few boxes contained objects
of the same shape, but of different colors
and sizes. Then, surprise! The f inal box con-
tin, y, t n cicl. If th bbi
had formed an overhypothesis based on
thi pviou xpincbox contin
items with the same shapethey should
have looked longer at this unexpected event.
An, in, thi w th c. Impotntly,
bbi fom ovhypoth qully wll
whn th itm in ch box w ll of th
same color but different shapes, showing thatthi lning mchnim i gnl n not,
say, the manifestation of an innate shape bias.
These experiments make it clear that
infnt cn cogniz pttn vy quickly
and use them to make generalizations at a very
early age. According to Xu, that suggests the
presence of a powerful learning mechanism
that might underlie many different biasesthat were previously thought to be innate.
Of course, it remains to be seen whether
thi mchnim i itlf ln th
over-overhypotheses to be discovered? In the
future, comparisons between overhypothesis
fomtion in infnt n tol my lo
help illuminate how this process changes
with age. If pattern recognition is something
that improves with practice, its possible that
young babies will have a harder time with
confusing cases than more experienced
toddlers and children; on the other hand,its also possible that the younger subjects
may actually have an easier time because
features Baby lab
Researchers can measure babies looking behavior to determine whether they find a particular event (here, a
sample of colored ping pong balls from a larger box with a different color distribution) to be expected or unexpected.JACqueliNeChretieN
AnotherdayattheInfantCognitionandLanguageLab...Wegetthebestone-linersfrompreschoolers.Ihadthispreschoolertoday,actually.Isaid...So,whydoyouthinkthatthatshowthisworks?Oh.IknowLOTSofthings.Oh,youdo?Ido.Ireallyknowalotofthings.Shesbarelyfour...
-StephanieDenison,PhDStudent
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24 Berkeley Science Review Spring 2011
thy hvnt yt ln to pivilg ctin
kin of infomtion ov oth.
Masters of probability
Early in January, I had a firsthand look atstudies investigating whether infants are
able to use statistical reasoning to predict
the likelihood of an event when my six-
month-old daughter, Ellie, participated in
n xpimnt in th Xu lb. Aft gtting
a basic rundown of the protocol from lab
mng n ch Chiti R n
signing some consent forms, we strapped
Ellie into a high chair facing what looked
lik puppt how tg in th xpimnt
oom. I w llow to ty, but h to tun
my bck to th xpimntl tup. Bbipay close attention to cues from their parents,
so any subtle shift in my behavior could have
skewed Ellies responses and invalidated the
ult. On th oth hn, bbi pon
to meltdowns when left alone in a strange
place. So: parents stay, but face away from
th tg.
While Ellie watched from her high chair,
Reed showed her a box containing a 4:1 ratio
of pink to yellow ping pong balls. (Other
versions of this study have used red, white or
gn bllcolo lct ntily b
us that they understand something about
om of th mpling poc, lik viul
access being important, random sampling
versus non-random sampling, those kinds
of thing, Dnion y. Eight-month-ol,
however, dont adjust their expectations
when the experimenter shows that they prefer pticul colo. Thi uggt ith tht
infants start to figure out other minds at
om point btwn ight n 11 month of
g, o tht it tk littl whil fo thm to
apply that filter to the probabilitic intuit ions
thy hv ly mt.
Another permutation of this experi-
mentin which Ellie also participated
this Februarylooks at how babies are
bl to clcult xpct pobbiliti.
Bbi w hown box contining th
colo of ping pong bll, on of which wimmobilized with Velcro. We teach them
that the ones with the Velcro dont move,
we obviously dont think they know any-
thing bout Vlco, xplin Dnion. Th
11-month-olds were able to integrate the new
infomtion, n xpct to mpl
that reflected only the remaining, mobile
balls, showing again that babies probability
estimates can be adjusted based on their
knowlg bout th phyicl wol.
Now, Dnion n oth in th lb
investigating how babies deal with a slightlymore sophisticated scheme, where some, but
not ll, bll of pticul colo immo-
biliz. Thi ffctivly qui th bbi
to multiply two probabilities together, which
should make it harder for them to predict
what a representative sample would look like.
Dtmining how wll bbi cn ti-
mate expected probabilities under many
kinds of conditions allows the researchers
to probe more deeply into how infants arrive
at these estimates. Humans are notorious for
failing to evaluate probabilities accurately,
on ping pong ball availability, says Denison,
on of th l ch on thi pojct).
After this demonstration, Reed took out
different samples of ping pong balls, and
filmed Ellies reaction when each samplewas revealed. Was she surprised when the
mpl contin fou yllow bll n on
pink bll, int of th oppoit?
We werent told her looking time results
(although, like most overbearing and/or
intellectually curious parents, I did ask), but
according to Reed, odds are pretty good that
she was surprised and her reaction reflected
it. The four-month-olds arent doing all that
well, she says, but so far the six-month-olds
o hv gp on it.
Amazingly, older infants can even adjusttheir expectations based on other sources
of information, from both the social and
physical realms. For example, if, prior to
the trial, the experimenter demonstrates
a preference for white balls, 11-month-old
bbi will uully look long t mpl
that doesnt match the researchers prefer-
nc, vn whn it mtch th contnt of
the box. More impressively, if the researcher
is blindfolded the 11-month olds know to
disregard the researchers preference and
expect a representative sample. This tells
features Baby lab
m
ArekJAkubowski
Kidswillletyouknowthatth
eythinkyourgameis
littleboring.Theyllsigh,they
llsay...
Arewealmostdone?Thisgam
estooeasyforme
Andtheyretotallybombing,b
uttheysay...
ImWAYtoosmartforthis,just
soyouknow.
-StephanieDenison,PhDStude
Graduate student researcher Stephanie Denison (left) tries to get the attention of a subject with a glowing pink
lollipop while mom looks on.
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Spring 2011 25Berkeley Science Review
depending on a variety of external factors
(the 10 percent of American homeowners
who unwt on thi motgg cn
tell you about the perils of optimism bias),
but not much i known bout why w mk
the mistakes we do. Studying whether babiesare susceptible to the same kinds of errors as
adults may help us solve this cognitive puzzle.
Come on over, baby
Whil looking tim i wll-pct n
frequently used experimental measure, it
cn b ticky in pctic. Looking bhvio
can be affected by many different factors, all
of which need to be controlled. Even then,
the difference between the reactions to an
expected and unexpected condition may only
b fw con. An of cou, no mtthow goo th y, it lwy nic to hv
a complementary experiment, particularly
on tht vy iffnt in ppoch.
With thi in min, th Xu lb h vl-
op novl, ctiv, n fnkly jut n
cool measure of babies thought processes:
cwling tow hin lollipop. Fo thi
assay, babies are first offered a black lollipop
and a pink lollipop; whichever one they reach
for or crawl to is established as the preferred
colo. Onc pfnc i tmin, th
babies are shown two boxes containing oppo-site ratios of pink to black, and the researcher
removes one lollipop from each container
in uch wy tht th bby cn only th
stick. If this were a looking time experiment,
the lollipops color would be revealed and the
bby ction woul b monito. In thi
new measure, however, the baby is allowed to
cwl o wlk to ith cup to how tht h
know which on i mo likly to contin
the preferred color. Eleven-month-olds pick
th ight cup bout 70 to 80 pcnt of th
time, showing that they have a reasonablyfim gp of ingl-vnt pobbility.
A with ny ch with bbi, how-
v, th cwling mu h it fi h
of ifficulti. Fit, it ifficult to b u
tht th bby h tu pfnc fo on
color. After all, babies can be fickle. The
initial experimental design called for four
preference trials, but the babies lost inter-
t by th tim th tt ti l oll oun,
making the results dif ficult to interpret. Its
always funny when as a researcher you think
youre doing this real ly intelligent, wonderful
task, and the baby should be so engaged, and
theyre like, hmm, I think Im just going
to go see whats over there on the door,
Denison says. Short attention spans have also
complicated the experiment in cuter ways.
Some babies, when asked to select a lollipop,choo to hug th xpimnt int.
So, th xpimnt ty to mk th
single preference trial really count. After
the selection is made, the researchers add
om poitiv infocmnt, clpping n
gnlly ncouging th bby to fl tht
shes made a truly excellent choice. (This
technique will also be familiar to anyone
who has ever tried to convince a skeptical
baby that she likes the new vegetable she
just tried.) And at the end of the experiment,
bbi hown j contining llpink or all black lollipops usu-
lly h fo th pf colo,
suggesting that the preference
is consistent throughout the
xpimnt.
Th ch lo nt
above using some tricks in an
ffot to chiv unifom colo
preference. The pink one
lights up now, which has made
it much, much, much easier to get basical ly
ll th bbi to pf pink, Dnion y.So far, this new method has been used to
show that babies not only understand which
bin is more likely to yield a pink pop, but
that they can apply this understanding to
guide their physical actions. Now, variations
on thi tup cn b u to pick pt ny
number of cognitive processes, including
overhypothesis formation. Its also much
easier to apply an active measure like this
to non-human animals (in fact, Denison
n Xu oiginlly cm up with th i
something that could be used with rhesusmcqu), n futu comptiv xpi-
ments are planned in monkeys and even
squirrels. These comparisons may help us
understand what makes human cognition
o uniqu.
Lab to life
The Xu labs insights into baby cognition are
fcinting in thi own ight, but th
lo pcticl ppliction fo thi ch.
Increasingly, computer scientists are col-
laborating with developmental psychologists
to create models of reasoning, learning, and
language acquisition that inform artificial
intelligence and natural language process-
ing. There are also applications in clinical
psychology. Infants performance in basic
cognitive tasks like these is increasinglyuntoo to b colt with thi bili-
ties later in life, so more detailed knowledge
of typical development may make it easier to
intify typicl vlopmnt t vy ly
stages, when interventions would be the most
ffctiv.
Nomlly vloping chiln cn bn-
fit fom nw inight, too. Knowing whn
specific cognitive skills are emerging can
help parents and educators engage with these
poc n giv chiln ich lning
environments. I feel that if youre aware
of this sort of thing, that could make youintct with th bby iffntly, o myb
provide different kinds of stimulation,
Yuan says. Personal experience bears this
outnow when Im browsing at the toy store,
Im on th lookout fo gm tht will chl-
lenge Ellies probabilistic reasoning skills.
An whn h ppoch th g t which
lngug cquiition xplo on th cn,
Ill b u to in in my u of xpltiv t
jut th ight tim.
Though major questions still remain,
and the nature versus nurture debate isincreasingly thought of as something of a
straw man, work from the Xu lab and others
in th fil h ctinly hown tht bbi
areas Denison puts itreally, really
smart. As a doting mom, this just confirms
what I already believed, but as a scientist? Its
nice to have some peer-reviewed citations to
bck m up.
Jacqueline Chretien is a graduate student in
molecular and cell biology.
features Baby lab
AnotherdayattheICLLab...Thecutestthingisseeingtheirlittlefaceswhentheykindofsquint,ortheyllbeperplexed.Youcanseetheyrethinking,theyrelooking....youcanjusttellthatintheirlittleminds,thegearsaregoing.-ChristieReed,Labmanager
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drowning in mu
by Keith Cheverallswith photo essay by Steve Axford
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scientit confront an ongoing eruption
The Lusi mud volcano devastates the landscape in Sidoarjo, Indonesia.
In the distance, steam rises from the volcanos vent.
Photograph by Craig Cooper
At 5:00m on My 29, 2006, int of th Inonin cityof Siojo wok to xploiv uption of g, wt, n
o much mu tht within y th nti villg w bui
up to its rooftops. Although devastating, the eruption would
hv bn mngblw it not fo th fct tht it h
never stopped. Nearly five years later, the eruption has anm, Lui, n h t co th lgt mu volcno
in the world. Since that May morning in 2006, Lusi has
jct n vg of 50,000 cubic mt of munough
to floo footbll fil to pth of tn mtvy y.
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28 Berkeley Science Review Spring 2011
e
uropeANpressphotoAgeNCy
features Mud volcanoes
After flowing for nearly five years, the
mu now cov ov ix qu kilomt
and has buried a dozen villages. Tens of
thousands of Indonesians, most of whom
were already poor, have seen their homes
and land destroyed, and thousands moreare threatened by the flow of mud, which,
while currently contained by a series of levees,
how no ign of topping.
Two competing explanations for
Lusis sudden eruption have emerged.
Measurements indicate that the mud is
coming from a vast, pressurized reservoir
about one and a half kilometers below the
surface. Geologists posit that a series of
pressure spikes in an exploratory natural
g wll 140 mt wy fom th volcno
perturbed the reservoir and triggered theeruption. Another theory, championed by
collapse under its own weight, forming a
crater-like depression that could destroy
even more of the surrounding communities?
Anphp th mot ugnt qution of
llwhn will th uption top?
The Berkeley connection
Michl Mng pk with tiking p-
cision and calm for someone who studies
some of the most b