berkeley science review - spring 2011

8/2/2019 Berkeley Science Review - Spring 2011

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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

Rachel Bernstein

Crystal Chaw

Mary Grace Lin

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Shirali Pandya

Josh Shiode

Art Director

Marek Jakubowski

Layout Staf

Kathryn Baldwin

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Katie Berry

Amy Orsborn

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Copy Editor

Hania Kver

Managing Editor

Mary Grace Lin

Web Editor

Anna Goldstein

Web Designers

Laura Fredriksen

Chris Holdgraf

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


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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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


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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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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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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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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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.


12/72


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


13/72

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


14/72


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


15/72


16/72


17/72


18/72

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


19/72


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


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).


20/72


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.


21/72


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


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


22/72


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


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.


23/72

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


24/72


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


25/72


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


26/72


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.


27/72


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


28/72

drowning in mu

by Keith Cheverallswith photo essay by Steve Axford


29/72

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.


30/72


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

berkeley science review - spring 2011

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