Table of contents

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Broken promises p503

Intense public support for clinical research can be a mixed blessing — and the hunt for a vaccine against AIDS offers an important lesson for many biomedical initiatives on what can go wrong.


Double vision p503

The need to transform the world's energy technology is even greater than many perceive.


Mismanaged measures p504

Surrogate end points can be helpful in clinical trials — but only if they are used with care.



Research Highlights

Research highlights p506



Journal Club

Journal club p507

A. P. de Silva




Are the IPCC scenarios 'unachievable'? p508

Claim that the challenge of cutting emissions has been underestimated is debated.

Quirin Schiermeier


Carbon-trading market has uncertain future p508

Clean development mechanism may be capped.

Jeff Tollefson


Drug markers questioned p510

A recent spate of worrying clinical-trial data has researchers questioning drugs approved on the basis of how they affect biomarkers rather than clinical endpoints. Heidi Ledford looks at surrogate markers.

Heidi Ledford


EPA feels heat over flame retardant p513

Dismissal of toxicologist raises concerns over delayed safety report.

Brian Vastag


Sidelines p514

Scribbles on the margins of science.


Easy ways to other Earths p514

Laser combs offer ground-based telescopes a chance to spot planetary homes from home.

Eric Hand


Snapshot: Flirty in pink p515

Dolphins turn on the charm.

Anna Petherick


Back to basics for HIV vaccine development p516


Tasting a geyser p516


US medical school to require master's degree p516


Too much haste in US drug approval? p516


Italy to help Kenya develop space programme p517


Muslim nations raise status of science p517


Correction p517




Hazy reasoning behind clean air p519

Science alone can't determine how regulations are written, argues David Goldston.

David Goldston



News Features

Architecture: Architects of a low-energy future p520

Low- and zero-energy buildings could have a huge impact on energy use and carbon emissions. We have the technologies, but if they are to mitigate climate change, green-building design must hit the mass market, says Declan Butler.


Anatomy: Truly gross anatomy p525

Sometimes it is necessary to immerse yourself in a subject. Erik Vance meets a woman whose research takes her deep — waist-deep — into cetacean anatomy.


Portugal: Navigating new waters p528

Portugal's spending on research is near the lowest in western Europe. Can a single-minded lady with half a billion euros change things, asks Alison Abbott.




Radical rethink is needed on climate-change policy p530

Gwyn Prins


Comparing the legacies of Gauss, Pasteur and Darwin p530

Jürgen Schmidhuber


Spanish funds will finance Bilbao's spallation bid p530

Juan Urrutia


Give south Indian authors their true names p530

Nalini Puniamoorthy, Jeevananthinee Jeevanandam & Sujatha Narayanan Kutty




Dangerous assumptions p531

How big is the energy challenge of climate change? The technological advances needed to stabilize carbon-dioxide emissions may be greater than we think, argue Roger Pielke Jr, Tom Wigley and Christopher Green.


See also: Editor's summary


Books and Arts

From spies to servers p533

Fastidious history chronicles how a suburb of Washington DC became home to the Internet.

Joel Shurkin reviews Internet Alley: High Technology in Tysons Corner, 1945–2005 by Paul E. Ceruzzi


Theatre: Ten years of science off Broadway p534

Alan Packer reviews


History: An astrolabe for the people p534

Philip Ball reviews


Film: Celluloid explores life of graduate student killer p535

Emma Marris



News and Views

Genomics: When the smoke clears ... p537

Three studies identify an association between genetic variation at a location on chromosome 15 and risk of lung cancer. But they disagree on whether the link is direct or mediated through nicotine dependence.

Stephen J. Chanock & David J. Hunter


See also: Editor's summary

Extrasolar planets: With a coarse-tooth comb p538

The search for Earth-like planets outside our Solar System is bedevilled by the lack of an adequate frequency standard for calibrating starlight. Tweaking existing laser 'frequency combs' could be a way forward.

Gordon Walker


See also: Editor's summary

Geophysics: Humming a different tune p539

Earth breathes in and out, murmuring gently to itself as it does so. The habit has been ascribed to the tickling effects of ocean waves — but a new-found twisting oscillation might reopen the search for the source.

Toshiro Tanimoto


Drug resistance: The fight against fungi p541

Although several drugs are available to combat often-deadly fungal infections, many of these pathogens have acquired multidrug resistance. Discerning how they have achieved this could help us hit back.

André Goffeau


See also: Editor's summary

Condensed-matter physics: Opposite of a superconductor p542

Magnetism and superconductivity are caused by spontaneous ordering on a macroscopic scale. Studies of a two-dimensional superconductor reveal another striking example of such behaviour — superinsulation.

Rosario Fazio


See also: Editor's summary

RNA interference: Generic block on angiogenesis p543

A virtue of using small interfering RNAs as therapeutics is their exquisite specificity. But when it comes to inhibiting blood-vessel growth, it seems that they can act generically without even entering a cell.

Raghu Kalluri & Keizo Kanasaki


See also: Editor's summary

Obituary: Arthur C. Clarke (1917–2008) p546

Visionary science-fiction author.

Gregory Benford



Insight: Molecular cancer diagnostics

Produced with support from:

Insight: Molecular cancer diagnostics

Molecular cancer diagnostics p547

Barbara Marte, Alex Eccleston & Deepa Nath


The cancer biomarker problem p548

Charles L. Sawyers


Translating insights from the cancer genome into clinical practice p553

Lynda Chin & Joe W. Gray


Enabling personalized cancer medicine through analysis of gene-expression patterns p564

Laura J. van 't Veer & René Bernards


Mining the plasma proteome for cancer biomarkers p571

Samir M. Hanash, Sharon J. Pitteri & Vitor M. Faca


Imaging in the era of molecular oncology p580

Ralph Weissleder & Mikael J. Pittet




Sequence- and target-independent angiogenesis suppression by siRNA via TLR3 p591

Mark E. Kleinman, Kiyoshi Yamada, Atsunobu Takeda, Vasu Chandrasekaran, Miho Nozaki, Judit Z. Baffi, Romulo J. C. Albuquerque, Satoshi Yamasaki, Masahiro Itaya, Yuzhen Pan, Binoy Appukuttan, Daniel Gibbs, Zhenglin Yang, Katalin Karikó, Balamurali K. Ambati, Traci A. Wilgus, Luisa A. DiPietro, Eiji Sakurai, Kang Zhang, Justine R. Smith, Ethan W. Taylor & Jayakrishna Ambati


See also: Editor's summary | News and Views by Kalluri & Kanasaki

Following translation by single ribosomes one codon at a time p598

Jin-Der Wen, Laura Lancaster, Courtney Hodges, Ana-Carolina Zeri, Shige H. Yoshimura, Harry F. Noller, Carlos Bustamante & Ignacio Tinoco


See also: Editor's summary

A nuclear receptor-like pathway regulating multidrug resistance in fungi p604

Jitendra K. Thakur, Haribabu Arthanari, Fajun Yang, Shih-Jung Pan, Xiaochun Fan, Julia Breger, Dominique P. Frueh, Kailash Gulshan, Darrick K. Li, Eleftherios Mylonakis, Kevin Struhl, W. Scott Moye-Rowley, Brendan P. Cormack, Gerhard Wagner & Anders M. Näär


See also: Editor's summary | News and Views by Goffeau



A laser frequency comb that enables radial velocity measurements with a precision of 1 cm s-1 p610

Chih-Hao Li, Andrew J. Benedick, Peter Fendel, Alexander G. Glenday, Franz X. Kärtner, David F. Phillips, Dimitar Sasselov, Andrew Szentgyorgyi & Ronald L. Walsworth


See also: Editor's summary | News and Views by Walker

Superinsulator and quantum synchronization p613

Valerii M. Vinokur, Tatyana I. Baturina, Mikhail V. Fistul, Aleksey Yu. Mironov, Mikhail R. Baklanov & Christoph Strunk


See also: Editor's summary | News and Views by Fazio

Dust-climate couplings over the past 800,000 years from the EPICA Dome C ice core p616

F. Lambert, B. Delmonte, J. R. Petit, M. Bigler, P. R. Kaufmann, M. A. Hutterli, T. F. Stocker, U. Ruth, J. P. Steffensen & V. Maggi


See also: Editor's summary

Absolute plate motions and true polar wander in the absence of hotspot tracks p620

Bernhard Steinberger & Trond H. Torsvik


Localization and functionality of microsporidian iron–sulphur cluster assembly proteins p624

Alina V. Goldberg, Sabine Molik, Anastasios D. Tsaousis, Karina Neumann, Grit Kuhnke, Frederic Delbac, Christian P. Vivares, Robert P. Hirt, Roland Lill & T. Martin Embley


See also: Editor's summary

Functional metagenomic profiling of nine biomes p629

Elizabeth A. Dinsdale, Robert A. Edwards, Dana Hall, Florent Angly, Mya Breitbart, Jennifer M. Brulc, Mike Furlan, Christelle Desnues, Matthew Haynes, Linlin Li, Lauren McDaniel, Mary Ann Moran, Karen E. Nelson, Christina Nilsson, Robert Olson, John Paul, Beltran Rodriguez Brito, Yijun Ruan, Brandon K. Swan, Rick Stevens, David L. Valentine, Rebecca Vega Thurber, Linda Wegley, Bryan A. White & Forest Rohwer


See also: Editor's summary

A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25 p633

Rayjean J. Hung, James D. McKay, Valerie Gaborieau, Paolo Boffetta, Mia Hashibe, David Zaridze, Anush Mukeria, Neonilia Szeszenia-Dabrowska, Jolanta Lissowska, Peter Rudnai, Eleonora Fabianova, Dana Mates, Vladimir Bencko, Lenka Foretova, Vladimir Janout, Chu Chen, Gary Goodman, John K. Field, Triantafillos Liloglou, George Xinarianos, Adrian Cassidy, John McLaughlin, Geoffrey Liu, Steven Narod, Hans E. Krokan, Frank Skorpen, Maiken Bratt Elvestad, Kristian Hveem, Lars Vatten, Jakob Linseisen, Françoise Clavel-Chapelon, Paolo Vineis, H. Bas Bueno-de-Mesquita, Eiliv Lund, Carmen Martinez, Sheila Bingham, Torgny Rasmuson, Pierre Hainaut, Elio Riboli, Wolfgang Ahrens, Simone Benhamou, Pagona Lagiou, Dimitrios Trichopoulos, Ivana Holcátová, Franco Merletti, Kristina Kjaerheim, Antonio Agudo, Gary Macfarlane, Renato Talamini, Lorenzo Simonato, Ray Lowry, David I. Conway, Ariana Znaor, Claire Healy, Diana Zelenika, Anne Boland, Marc Delepine, Mario Foglio, Doris Lechner, Fumihiko Matsuda, Helene Blanche, Ivo Gut, Simon Heath, Mark Lathrop & Paul Brennan


See also: Editor's summary | News and Views by Chanock & Hunter

A variant associated with nicotine dependence, lung cancer and peripheral arterial disease p638

Thorgeir E. Thorgeirsson, Frank Geller, Patrick Sulem, Thorunn Rafnar, Anna Wiste, Kristinn P. Magnusson, Andrei Manolescu, Gudmar Thorleifsson, Hreinn Stefansson, Andres Ingason, Simon N. Stacey, Jon T. Bergthorsson, Steinunn Thorlacius, Julius Gudmundsson, Thorlakur Jonsson, Margret Jakobsdottir, Jona Saemundsdottir, Olof Olafsdottir, Larus J. Gudmundsson, Gyda Bjornsdottir, Kristleifur Kristjansson, Halla Skuladottir, Helgi J. Isaksson, Tomas Gudbjartsson, Gregory T. Jones, Thomas Mueller, Anders Gottsäter, Andrea Flex, Katja K. H. Aben, Femmie de Vegt, Peter F. A. Mulders, Dolores Isla, Maria J. Vidal, Laura Asin, Berta Saez, Laura Murillo, Thorsteinn Blondal, Halldor Kolbeinsson, Jon G. Stefansson, Ingunn Hansdottir, Valgerdur Runarsdottir, Roberto Pola, Bengt Lindblad, Andre M. van Rij, Benjamin Dieplinger, Meinhard Haltmayer, Jose I. Mayordomo, Lambertus A. Kiemeney, Stefan E. Matthiasson, Hogni Oskarsson, Thorarinn Tyrfingsson, Daniel F. Gudbjartsson, Jeffrey R. Gulcher, Steinn Jonsson, Unnur Thorsteinsdottir, Augustine Kong & Kari Stefansson


See also: Editor's summary | News and Views by Chanock & Hunter

A neural representation of depth from motion parallax in macaque visual cortex p642

Jacob W. Nadler, Dora E. Angelaki & Gregory C. DeAngelis


See also: Editor's summary

Tumour maintenance is mediated by eNOS p646

Kian-Huat Lim, Brooke B. Ancrile, David F. Kashatus & Christopher M. Counter


Cutaneous cancer stem cell maintenance is dependent on beta-catenin signalling p650

Ilaria Malanchi, Hector Peinado, Deepika Kassen, Thomas Hussenet, Daniel Metzger, Pierre Chambon, Marcel Huber, Daniel Hohl, Amparo Cano, Walter Birchmeier & Joerg Huelsken


See also: Editor's summary

Dendritic cell PAR1–S1P3 signalling couples coagulation and inflammation p654

Frank Niessen, Florence Schaffner, Christian Furlan-Freguia, Rafal Pawlinski, Gourab Bhattacharjee, Jerold Chun, Claudia K. Derian, Patricia Andrade-Gordon, Hugh Rosen & Wolfram Ruf





Prospects p659

The startling contrasts of Bangalore

Gene Russo



Biotech in Bangalore p660

Bangalore has a growing biotech sector, supported by a tradition of academic science. But there are still challenges in committing to discovery science and retaining top talent. Gene Russo reports.

Gene Russo


Career View

Dave Tapolczay, chief executive, MRC Technology, London p662

Tapolczay looking to bolster MRC tech transfer

Jill U. Adams


Göttingen bridges the gap p662

Max Planck gets complex with new degree programme.

Virginia Gewin


Getting that lucky break p662

My project isn't working. Is it OK to quit?

Amanda Goh




Shoppers p664

No purchase necessary.

James Patrick Kelly


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