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Fig. 6. cGAS binds to DNA in the cytoplasm. (A) Nuclear and cytoplasmic fractions were prepared from<br />

THP-1 cells and an<strong>al</strong>yzed by immunoblotting with the indicated antibodies. (B) THP-1 cells were<br />

homogenized in hypotonic buffer and subjected to differenti<strong>al</strong> centrifugation. Pell<strong>et</strong>s at different speeds<br />

of centrifugation (e.g., P100: pell<strong>et</strong>s after 100,000g) and S100 were immunoblotted with the indicated<br />

antibodies. (C) L929 cells stably expressing Flag-cGAS (green) were transfected with Cy3-ISD (red). At<br />

different time points after transfection, cells were fixed, stained with antibody to Flag or with 4´,6diamidino-2-phenylindole<br />

(DAPI), and imaged by confoc<strong>al</strong> fluorescence microscopy. The ins<strong>et</strong>s in the<br />

merged images are magnifications of the sm<strong>al</strong>l boxed areas. These images are representative of at least<br />

10 cells at each time point (representing >50% of the cells under examination).<br />

into the host cytoplasm—such as DNA viruses,<br />

bacteria, parasites (e.g., m<strong>al</strong>aria), and r<strong>et</strong>roviruses<br />

(e.g., HIV)—could potenti<strong>al</strong>ly trigger the cGAS-<br />

STING pathway (14, 15). The enzymatic synthesis<br />

of cGAMP by cGAS provides a mechanism<br />

of sign<strong>al</strong> amplification for a robust and sensitive<br />

immune response. However, the d<strong>et</strong>ection of self<br />

DNA in the host cytoplasm by cGAS could <strong>al</strong>so<br />

lead to autoimmune diseases, such as systemic<br />

lupus erythematosus, Sjögren’s syndrome, and<br />

Aicardi-Goutières syndrome (16–18).<br />

Sever<strong>al</strong> other DNA sensors, such as DAI,<br />

IFI16, and DDX41, have been reported to in-<br />

Univers<strong>al</strong> Computation by<br />

Multiparticle Quantum W<strong>al</strong>k<br />

Andrew M. Childs, 1,2 David Goss<strong>et</strong>, 1,2 * Zak Webb 2,3<br />

duce type I interferons (19–21). Overexpression<br />

of DAI, IFI16, or DDX41 did not lead to<br />

the production of cGAMP. We <strong>al</strong>so found that<br />

knockdown of DDX41 and p204 (a mouse homolog<br />

of IFI16) by siRNA did not inhibit the<br />

generation of cGAMP activity in HT-DNA–<br />

transfected L929 cells (fig. S7). Non<strong>et</strong>heless, it<br />

is possible that distinct DNA sensors exist in different<br />

cell types. Unlike other putative DNA<br />

sensors and most pattern recognition receptors<br />

(e.g., TLRs), cGAS is a cyclase that is likely more<br />

amenable to inhibition by sm<strong>al</strong>l-molecule compounds.<br />

These inhibitors may be developed into<br />

A quantum w<strong>al</strong>k is a time-homogeneous quantum-mechanic<strong>al</strong> process on a graph defined by an<strong>al</strong>ogy to<br />

classic<strong>al</strong> random w<strong>al</strong>k. The quantum w<strong>al</strong>ker is a particle that moves from a given vertex to adjacent<br />

vertices in quantum superposition. We consider a gener<strong>al</strong>ization to interacting systems with more than<br />

onew<strong>al</strong>ker,suchastheBose-Hubbardmodelandsystems of fermions or distinguishable particles with<br />

nearest-neighbor interactions, and show that multiparticle quantum w<strong>al</strong>k is capable of univers<strong>al</strong> quantum<br />

computation. Our construction could, in principle, be used as an architecture for building a sc<strong>al</strong>able<br />

quantum computer with no need for time-dependent control.<br />

Quantum w<strong>al</strong>k is a versatile and intuitive<br />

framework for developing quantum <strong>al</strong>gorithms.<br />

Applications of continuous- (1)<br />

and discr<strong>et</strong>e-time (2, 3) models of quantum w<strong>al</strong>k<br />

include an example of exponenti<strong>al</strong> speed-up over<br />

classic<strong>al</strong> computation (4) and optim<strong>al</strong> <strong>al</strong>go-<br />

therapeutic agents for the treatment of human<br />

autoimmune diseases.<br />

References and Notes<br />

1. L. A. O’Neill, Cell 138, 428 (2009).<br />

2. G. N. Barber, Immunol. Rev. 243, 99 (2011).<br />

3. S. E. Keating, M. Baran, A. G. Bowie, Trends Immunol.<br />

32, 574 (2011).<br />

4. J. Wu <strong>et</strong> <strong>al</strong>., Science 339, 826 (2013).<br />

5. J. Cox, M. Mann, Nat. Biotechnol. 26, 1367 (2008).<br />

6. K. Kuchta, L. Knizewski, L. S. Wyrwicz, L. Rychlewski,<br />

K. Gin<strong>al</strong>ski, Nucleic Acids Res. 37, 7701 (2009).<br />

7. K. L. Chow, D. H. H<strong>al</strong>l, S. W. Emmons, Development 121,<br />

3615 (1995).<br />

8. J. Pei, B. H. Kim, N. V. Grishin, Nucleic Acids Res. 36,<br />

2295 (2008).<br />

9. J. W. Schoggins <strong>et</strong> <strong>al</strong>., Nature 472, 481 (2011).<br />

10. Y. H. Chiu, J. B. Macmillan, Z. J. Chen, Cell 138, 576 (2009).<br />

11. C. Pesavento, R. Hengge, Curr. Opin. Microbiol. 12, 170<br />

(2009).<br />

12. B. W. Davies, R. W. Bogard, T. S. Young, J. J. Mek<strong>al</strong>anos,<br />

Cell 149, 358 (2012).<br />

13. Z. H. Chen, P. Schaap, Nature 488, 680 (2012).<br />

14. S. Sharma <strong>et</strong> <strong>al</strong>., Immunity 35, 194 (2011).<br />

15. N. Yan, Z. J. Chen, Nat. Immunol. 13, 214 (2012).<br />

16. V. Pascu<strong>al</strong>, L. Farkas, J. Banchereau, Curr. Opin.<br />

Immunol. 18, 676 (2006).<br />

17. Y. Yao, Z. Liu, B. J<strong>al</strong>l<strong>al</strong>, N. Shen, L. Ronnblom, Autoimmun.<br />

Rev. 10.1016/j.autrev.2012.10.006 (2012).<br />

18. R. E. Rigby, A. Leitch, A. P. Jackson, Bioessays 30, 833 (2008).<br />

19. A. Takaoka <strong>et</strong> <strong>al</strong>., Nature 448, 501 (2007).<br />

20. L. Unterholzner <strong>et</strong> <strong>al</strong>., Nat. Immunol. 11, 997 (2010).<br />

21. Z. Zhang <strong>et</strong> <strong>al</strong>., Nat. Immunol. 12, 959 (2011).<br />

Acknowledgments: W<strong>et</strong>hankW.Liforhelpfuldiscussion<br />

on bioinformatics an<strong>al</strong>yses. The GenBank accession numbers<br />

for human and mouse cGAS sequences are KC294566 and<br />

KC294567, respectively. Supported by NIH grant AI-093967.<br />

Z.J.C. is an investigator of Howard Hughes Medic<strong>al</strong> Institute.<br />

Supplementary Materi<strong>al</strong>s<br />

www.sciencemag.org/cgi/content/full/science.1232458/DC1<br />

Materi<strong>al</strong>s and M<strong>et</strong>hods<br />

Figs. S1 to S7<br />

Table S1<br />

References (22, 23)<br />

7 November 2012; accepted 12 December 2012<br />

Published online 20 December 2012;<br />

10.1126/science.1232458<br />

REPORTS<br />

rithms for element distinctness (5) and formula<br />

ev<strong>al</strong>uation (6).<br />

Quantum w<strong>al</strong>k is <strong>al</strong>so a powerful computation<strong>al</strong><br />

model capable of performing any quantum<br />

computation (7). However, the graph used to perform<br />

a computation on n qubits is exponenti<strong>al</strong>ly<br />

large as a function of n. Such a quantum w<strong>al</strong>k<br />

cannot be efficiently implemented using an architecture<br />

where each vertex of the graph occupies<br />

a different spati<strong>al</strong> location. Nevertheless, many<br />

nonsc<strong>al</strong>able implementations of quantum w<strong>al</strong>k<br />

have been carried out (8–10) despite substanti<strong>al</strong><br />

1<br />

Department of Combinatorics and Optimization, University of<br />

Waterloo, Waterloo, Ontario N2L 3G1, Canada. 2 Institute for<br />

Quantum Computing, University of Waterloo, Waterloo, Ontario<br />

N2L 3G1, Canada. 3 Department of Physics and Astronomy,<br />

University of Waterloo, Waterloo, Ontario N2L 3G1, Canada.<br />

*To whom correspondence should be addressed. E-mail:<br />

dngoss<strong>et</strong>@gmail.com<br />

www.sciencemag.org SCIENCE VOL 339 15 FEBRUARY 2013 791<br />

on February 14, 2013<br />

www.sciencemag.org<br />

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