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Items: 1 to 50 of 219

1.

Solid stress in brain tumours causes neuronal loss and neurological dysfunction and can be reversed by lithium.

Seano G, Nia HT, Emblem KE, Datta M, Ren J, Krishnan S, Kloepper J, Pinho MC, Ho WW, Ghosh M, Askoxylakis V, Ferraro GB, Riedemann L, Gerstner ER, Batchelor TT, Wen PY, Lin NU, Grodzinsky AJ, Fukumura D, Huang P, Baish JW, Padera TP, Munn LL, Jain RK.

Nat Biomed Eng. 2019 Mar;3(3):230-245. doi: 10.1038/s41551-018-0334-7. Epub 2019 Jan 7.

2.

Retraction Note: A homing system targets therapeutic T cells to brain cancer.

Samaha H, Pignata A, Fousek K, Ren J, Lam FW, Stossi F, Dubrulle J, Salsman VS, Krishnan S, Hong SH, Baker ML, Shree A, Gad AZ, Shum T, Fukumura D, Byrd TT, Mukherjee M, Marrelli SP, Orange JS, Joseph SK, Sorensen PH, Taylor MD, Hegde M, Mamonkin M, Jain RK, El-Naggar S, Ahmed N.

Nature. 2019 Mar;567(7746):132. doi: 10.1038/s41586-019-0967-z.

3.

Experimental and computational analyses reveal dynamics of tumor vessel cooption and optimal treatment strategies.

Voutouri C, Kirkpatrick ND, Chung E, Mpekris F, Baish JW, Munn LL, Fukumura D, Stylianopoulos T, Jain RK.

Proc Natl Acad Sci U S A. 2019 Feb 12;116(7):2662-2671. doi: 10.1073/pnas.1818322116. Epub 2019 Jan 30.

PMID:
30700544
4.

Dual endothelin receptor inhibition enhances T-DM1 efficacy in brain metastases from HER2-positive breast cancer.

Askoxylakis V, Ferraro GB, Badeaux M, Kodack DP, Kirst I, Shankaraiah RC, Wong CSF, Duda DG, Fukumura D, Jain RK.

NPJ Breast Cancer. 2019 Jan 15;5:4. doi: 10.1038/s41523-018-0100-8. eCollection 2019.

5.

A homing system targets therapeutic T cells to brain cancer.

Samaha H, Pignata A, Fousek K, Ren J, Lam FW, Stossi F, Dubrulle J, Salsman VS, Krishnan S, Hong SH, Baker ML, Shree A, Gad AZ, Shum T, Fukumura D, Byrd TT, Mukherjee M, Marrelli SP, Orange JS, Joseph SK, Sorensen PH, Taylor MD, Hegde M, Mamonkin M, Jain RK, El-Naggar S, Ahmed N.

Nature. 2018 Sep;561(7723):331-337. doi: 10.1038/s41586-018-0499-y. Epub 2018 Sep 5. Retraction in: Nature. 2019 Mar;567(7746):132.

6.

Mechanisms of enhanced drug delivery in brain metastases with focused ultrasound-induced blood-tumor barrier disruption.

Arvanitis CD, Askoxylakis V, Guo Y, Datta M, Kloepper J, Ferraro GB, Bernabeu MO, Fukumura D, McDannold N, Jain RK.

Proc Natl Acad Sci U S A. 2018 Sep 11;115(37):E8717-E8726. doi: 10.1073/pnas.1807105115. Epub 2018 Aug 27.

7.

Consensus guidelines for the use and interpretation of angiogenesis assays.

Nowak-Sliwinska P, Alitalo K, Allen E, Anisimov A, Aplin AC, Auerbach R, Augustin HG, Bates DO, van Beijnum JR, Bender RHF, Bergers G, Bikfalvi A, Bischoff J, Böck BC, Brooks PC, Bussolino F, Cakir B, Carmeliet P, Castranova D, Cimpean AM, Cleaver O, Coukos G, Davis GE, De Palma M, Dimberg A, Dings RPM, Djonov V, Dudley AC, Dufton NP, Fendt SM, Ferrara N, Fruttiger M, Fukumura D, Ghesquière B, Gong Y, Griffin RJ, Harris AL, Hughes CCW, Hultgren NW, Iruela-Arispe ML, Irving M, Jain RK, Kalluri R, Kalucka J, Kerbel RS, Kitajewski J, Klaassen I, Kleinmann HK, Koolwijk P, Kuczynski E, Kwak BR, Marien K, Melero-Martin JM, Munn LL, Nicosia RF, Noel A, Nurro J, Olsson AK, Petrova TV, Pietras K, Pili R, Pollard JW, Post MJ, Quax PHA, Rabinovich GA, Raica M, Randi AM, Ribatti D, Ruegg C, Schlingemann RO, Schulte-Merker S, Smith LEH, Song JW, Stacker SA, Stalin J, Stratman AN, Van de Velde M, van Hinsbergh VWM, Vermeulen PB, Waltenberger J, Weinstein BM, Xin H, Yetkin-Arik B, Yla-Herttuala S, Yoder MC, Griffioen AW.

Angiogenesis. 2018 Aug;21(3):425-532. doi: 10.1007/s10456-018-9613-x. Review.

8.

Shortwave infrared fluorescence imaging with the clinically approved near-infrared dye indocyanine green.

Carr JA, Franke D, Caram JR, Perkinson CF, Saif M, Askoxylakis V, Datta M, Fukumura D, Jain RK, Bawendi MG, Bruns OT.

Proc Natl Acad Sci U S A. 2018 Apr 24;115(17):4465-4470. doi: 10.1073/pnas.1718917115. Epub 2018 Apr 6.

9.

Obesity promotes resistance to anti-VEGF therapy in breast cancer by up-regulating IL-6 and potentially FGF-2.

Incio J, Ligibel JA, McManus DT, Suboj P, Jung K, Kawaguchi K, Pinter M, Babykutty S, Chin SM, Vardam TD, Huang Y, Rahbari NN, Roberge S, Wang D, Gomes-Santos IL, Puchner SB, Schlett CL, Hoffmman U, Ancukiewicz M, Tolaney SM, Krop IE, Duda DG, Boucher Y, Fukumura D, Jain RK.

Sci Transl Med. 2018 Mar 14;10(432). pii: eaag0945. doi: 10.1126/scitranslmed.aag0945.

10.

Enhancing cancer immunotherapy using antiangiogenics: opportunities and challenges.

Fukumura D, Kloepper J, Amoozgar Z, Duda DG, Jain RK.

Nat Rev Clin Oncol. 2018 May;15(5):325-340. doi: 10.1038/nrclinonc.2018.29. Epub 2018 Mar 6. Review.

11.

Functional Anti-TIGIT Antibodies Regulate Development of Autoimmunity and Antitumor Immunity.

Dixon KO, Schorer M, Nevin J, Etminan Y, Amoozgar Z, Kondo T, Kurtulus S, Kassam N, Sobel RA, Fukumura D, Jain RK, Anderson AC, Kuchroo VK, Joller N.

J Immunol. 2018 Apr 15;200(8):3000-3007. doi: 10.4049/jimmunol.1700407. Epub 2018 Mar 2.

12.

Wide-field three-photon excitation in biological samples.

Rowlands CJ, Park D, Bruns OT, Piatkevich KD, Fukumura D, Jain RK, Bawendi MG, Boyden ES, So PT.

Light Sci Appl. 2017 May 5;6:e16255. doi: 10.1038/lsa.2016.255.

13.

Next-generation in vivo optical imaging with short-wave infrared quantum dots.

Bruns OT, Bischof TS, Harris DK, Franke D, Shi Y, Riedemann L, Bartelt A, Jaworski FB, Carr JA, Rowlands CJ, Wilson MWB, Chen O, Wei H, Hwang GW, Montana DM, Coropceanu I, Achorn OB, Kloepper J, Heeren J, So PTC, Fukumura D, Jensen KF, Jain RK, Bawendi MG.

Nat Biomed Eng. 2017;1. pii: 0056. doi: 10.1038/s41551-017-0056. Epub 2017 Apr 10.

14.

MicroRNA-378 enhances radiation response in ectopic and orthotopic implantation models of glioblastoma.

Li W, Liu Y, Yang W, Han X, Li S, Liu H, Gerweck LE, Fukumura D, Loeffler JS, Yang BB, Jain RK, Huang P.

J Neurooncol. 2018 Jan;136(1):63-71. doi: 10.1007/s11060-017-2646-y. Epub 2017 Oct 28.

15.

A cerebellar window for intravital imaging of normal and disease states in mice.

Askoxylakis V, Badeaux M, Roberge S, Batista A, Kirkpatrick N, Snuderl M, Amoozgar Z, Seano G, Ferraro GB, Chatterjee S, Xu L, Fukumura D, Duda DG, Jain RK.

Nat Protoc. 2017 Nov;12(11):2251-2262. doi: 10.1038/nprot.2017.101. Epub 2017 Oct 5.

16.

Targeting CXCR4-dependent immunosuppressive Ly6Clow monocytes improves antiangiogenic therapy in colorectal cancer.

Jung K, Heishi T, Incio J, Huang Y, Beech EY, Pinter M, Ho WW, Kawaguchi K, Rahbari NN, Chung E, Kim JK, Clark JW, Willett CG, Yun SH, Luster AD, Padera TP, Jain RK, Fukumura D.

Proc Natl Acad Sci U S A. 2017 Sep 26;114(39):10455-10460. doi: 10.1073/pnas.1710754114. Epub 2017 Sep 12.

17.

Ly6Clo monocytes drive immunosuppression and confer resistance to anti-VEGFR2 cancer therapy.

Jung K, Heishi T, Khan OF, Kowalski PS, Incio J, Rahbari NN, Chung E, Clark JW, Willett CG, Luster AD, Yun SH, Langer R, Anderson DG, Padera TP, Jain RK, Fukumura D.

J Clin Invest. 2017 Aug 1;127(8):3039-3051. doi: 10.1172/JCI93182. Epub 2017 Jul 10.

18.

The brain microenvironment mediates resistance in luminal breast cancer to PI3K inhibition through HER3 activation.

Kodack DP, Askoxylakis V, Ferraro GB, Sheng Q, Badeaux M, Goel S, Qi X, Shankaraiah R, Cao ZA, Ramjiawan RR, Bezwada D, Patel B, Song Y, Costa C, Naxerova K, Wong CSF, Kloepper J, Das R, Tam A, Tanboon J, Duda DG, Miller CR, Siegel MB, Anders CK, Sanders M, Estrada MV, Schlegel R, Arteaga CL, Brachtel E, Huang A, Fukumura D, Engelman JA, Jain RK.

Sci Transl Med. 2017 May 24;9(391). pii: eaal4682. doi: 10.1126/scitranslmed.aal4682. Erratum in: Sci Transl Med. 2019 Jan 30;11(477):.

19.

Corrigendum: Reengineering the Tumor Microenvironment to Alleviate Hypoxia and Overcome Cancer Heterogeneity.

Martin JD, Fukumura D, Duda DG, Boucher Y, Jain RK.

Cold Spring Harb Perspect Med. 2016 Dec 1;6(12). pii: a031195. doi: 10.1101/cshperspect.a031195. No abstract available.

20.

Anti-VEGF therapy induces ECM remodeling and mechanical barriers to therapy in colorectal cancer liver metastases.

Rahbari NN, Kedrin D, Incio J, Liu H, Ho WW, Nia HT, Edrich CM, Jung K, Daubriac J, Chen I, Heishi T, Martin JD, Huang Y, Maimon N, Reissfelder C, Weitz J, Boucher Y, Clark JW, Grodzinsky AJ, Duda DG, Jain RK, Fukumura D.

Sci Transl Med. 2016 Oct 12;8(360):360ra135.

21.

Reengineering the Tumor Microenvironment to Alleviate Hypoxia and Overcome Cancer Heterogeneity.

Martin JD, Fukumura D, Duda DG, Boucher Y, Jain RK.

Cold Spring Harb Perspect Med. 2016 Dec 1;6(12). pii: a027094. doi: 10.1101/cshperspect.a027094. Review. Erratum in: Cold Spring Harb Perspect Med. 2016 Dec 1;6(12 ):.

22.

Measuring Vascular Permeability In Vivo.

Meijer EF, Baish JW, Padera TP, Fukumura D.

Methods Mol Biol. 2016;1458:71-85. doi: 10.1007/978-1-4939-3801-8_6.

23.

Obesity-Induced Inflammation and Desmoplasia Promote Pancreatic Cancer Progression and Resistance to Chemotherapy.

Incio J, Liu H, Suboj P, Chin SM, Chen IX, Pinter M, Ng MR, Nia HT, Grahovac J, Kao S, Babykutty S, Huang Y, Jung K, Rahbari NN, Han X, Chauhan VP, Martin JD, Kahn J, Huang P, Desphande V, Michaelson J, Michelakos TP, Ferrone CR, Soares R, Boucher Y, Fukumura D, Jain RK.

Cancer Discov. 2016 Aug;6(8):852-69. doi: 10.1158/2159-8290.CD-15-1177. Epub 2016 May 31.

24.

Arginine dependence of tumor cells: targeting a chink in cancer's armor.

Patil MD, Bhaumik J, Babykutty S, Banerjee UC, Fukumura D.

Oncogene. 2016 Sep 22;35(38):4957-72. doi: 10.1038/onc.2016.37. Epub 2016 Apr 25. Review.

25.

Ang-2/VEGF bispecific antibody reprograms macrophages and resident microglia to anti-tumor phenotype and prolongs glioblastoma survival.

Kloepper J, Riedemann L, Amoozgar Z, Seano G, Susek K, Yu V, Dalvie N, Amelung RL, Datta M, Song JW, Askoxylakis V, Taylor JW, Lu-Emerson C, Batista A, Kirkpatrick ND, Jung K, Snuderl M, Muzikansky A, Stubenrauch KG, Krieter O, Wakimoto H, Xu L, Munn LL, Duda DG, Fukumura D, Batchelor TT, Jain RK.

Proc Natl Acad Sci U S A. 2016 Apr 19;113(16):4476-81. doi: 10.1073/pnas.1525360113. Epub 2016 Apr 4.

26.

Dual inhibition of Ang-2 and VEGF receptors normalizes tumor vasculature and prolongs survival in glioblastoma by altering macrophages.

Peterson TE, Kirkpatrick ND, Huang Y, Farrar CT, Marijt KA, Kloepper J, Datta M, Amoozgar Z, Seano G, Jung K, Kamoun WS, Vardam T, Snuderl M, Goveia J, Chatterjee S, Batista A, Muzikansky A, Leow CC, Xu L, Batchelor TT, Duda DG, Fukumura D, Jain RK.

Proc Natl Acad Sci U S A. 2016 Apr 19;113(16):4470-5. doi: 10.1073/pnas.1525349113. Epub 2016 Apr 4.

27.

PlGF/VEGFR-1 Signaling Promotes Macrophage Polarization and Accelerated Tumor Progression in Obesity.

Incio J, Tam J, Rahbari NN, Suboj P, McManus DT, Chin SM, Vardam TD, Batista A, Babykutty S, Jung K, Khachatryan A, Hato T, Ligibel JA, Krop IE, Puchner SB, Schlett CL, Hoffmman U, Ancukiewicz M, Shibuya M, Carmeliet P, Soares R, Duda DG, Jain RK, Fukumura D.

Clin Cancer Res. 2016 Jun 15;22(12):2993-3004. doi: 10.1158/1078-0432.CCR-15-1839. Epub 2016 Feb 9.

28.

Obesity and Cancer: An Angiogenic and Inflammatory Link.

Fukumura D, Incio J, Shankaraiah RC, Jain RK.

Microcirculation. 2016 Apr;23(3):191-206. doi: 10.1111/micc.12270. Review.

29.

Mast Cells Contribute to Radiation-Induced Vascular Hyperpermeability.

Park KR, Monsky WL, Lee CG, Song CH, Kim DH, Jain RK, Fukumura D.

Radiat Res. 2016 Feb;185(2):182-9. doi: 10.1667/RR14190.1. Epub 2016 Jan 15.

30.

A mouse-human phase 1 co-clinical trial of a protease-activated fluorescent probe for imaging cancer.

Whitley MJ, Cardona DM, Lazarides AL, Spasojevic I, Ferrer JM, Cahill J, Lee CL, Snuderl M, Blazer DG 3rd, Hwang ES, Greenup RA, Mosca PJ, Mito JK, Cuneo KC, Larrier NA, O'Reilly EK, Riedel RF, Eward WC, Strasfeld DB, Fukumura D, Jain RK, Lee WD, Griffith LG, Bawendi MG, Kirsch DG, Brigman BE.

Sci Transl Med. 2016 Jan 6;8(320):320ra4. doi: 10.1126/scitranslmed.aad0293.

31.

Solid stress and elastic energy as measures of tumour mechanopathology.

Nia HT, Liu H, Seano G, Datta M, Jones D, Rahbari N, Incio J, Chauhan VP, Jung K, Martin JD, Askoxylakis V, Padera TP, Fukumura D, Boucher Y, Hornicek FJ, Grodzinsky AJ, Baish JW, Munn LL, Jain RK.

Nat Biomed Eng. 2016;1. pii: 0004. doi: 10.1038/s41551-016-0004. Epub 2016 Nov 28.

32.

Mouse embryonic fibroblasts exhibit extensive developmental and phenotypic diversity.

Singhal PK, Sassi S, Lan L, Au P, Halvorsen SC, Fukumura D, Jain RK, Seed B.

Proc Natl Acad Sci U S A. 2016 Jan 5;113(1):122-7. doi: 10.1073/pnas.1522401112. Epub 2015 Dec 22.

33.

Metformin Reduces Desmoplasia in Pancreatic Cancer by Reprogramming Stellate Cells and Tumor-Associated Macrophages.

Incio J, Suboj P, Chin SM, Vardam-Kaur T, Liu H, Hato T, Babykutty S, Chen I, Deshpande V, Jain RK, Fukumura D.

PLoS One. 2015 Dec 7;10(12):e0141392. doi: 10.1371/journal.pone.0141392. eCollection 2015.

34.

Preclinical Efficacy of Ado-trastuzumab Emtansine in the Brain Microenvironment.

Askoxylakis V, Ferraro GB, Kodack DP, Badeaux M, Shankaraiah RC, Seano G, Kloepper J, Vardam T, Martin JD, Naxerova K, Bezwada D, Qi X, Selig MK, Brachtel E, Duda DG, Huang P, Fukumura D, Engelman JA, Jain RK.

J Natl Cancer Inst. 2015 Nov 7;108(2). pii: djv313. doi: 10.1093/jnci/djv313. Print 2016 Feb.

35.

Vascular diseases await translation of blood vessels engineered from stem cells.

Samuel R, Duda DG, Fukumura D, Jain RK.

Sci Transl Med. 2015 Oct 14;7(309):309rv6. doi: 10.1126/scitranslmed.aaa1805. Review.

36.

From the Guest Editors: Role of Tumor Microenvironment in Tumor Progression and Treatment Response: A 30 Years' Journey.

Jain RK, Fukumura D, Duda DG.

Cancer J. 2015 Jul-Aug;21(4):235-6. doi: 10.1097/PPO.0000000000000136. No abstract available.

37.

Micelle-Encapsulated Quantum Dot-Porphyrin Assemblies as in Vivo Two-Photon Oxygen Sensors.

Lemon CM, Karnas E, Han X, Bruns OT, Kempa TJ, Fukumura D, Bawendi MG, Jain RK, Duda DG, Nocera DG.

J Am Chem Soc. 2015 Aug 12;137(31):9832-42. doi: 10.1021/jacs.5b04765. Epub 2015 Jul 29.

38.

Lessons From 30 Years of Teaching About the Microenvironment of Tumors.

Jain RK, Fukumura D, Duda DG.

Cancer J. 2015 May-Jun;21(3):137. doi: 10.1097/PPO.0000000000000119. No abstract available.

39.

Longitudinal Tracing of Spontaneous Regression and Anti-angiogenic Response of Individual Microadenomas during Colon Tumorigenesis.

Choi JW, Kim P, Kim JK, Kim YR, Fukumura D, Yun SH.

Theranostics. 2015 Apr 1;5(7):724-32. doi: 10.7150/thno.10734. eCollection 2015.

40.

Blockade of MMP14 activity in murine breast carcinomas: implications for macrophages, vessels, and radiotherapy.

Ager EI, Kozin SV, Kirkpatrick ND, Seano G, Kodack DP, Askoxylakis V, Huang Y, Goel S, Snuderl M, Muzikansky A, Finkelstein DM, Dransfield DT, Devy L, Boucher Y, Fukumura D, Jain RK.

J Natl Cancer Inst. 2015 Feb 20;107(4). pii: djv017. doi: 10.1093/jnci/djv017. Print 2015 Apr.

41.

Towards Optimal Design of Cancer Nanomedicines: Multi-stage Nanoparticles for the Treatment of Solid Tumors.

Stylianopoulos T, Economides EA, Baish JW, Fukumura D, Jain RK.

Ann Biomed Eng. 2015 Sep;43(9):2291-300. doi: 10.1007/s10439-015-1276-9. Epub 2015 Feb 11.

42.

Emerging strategies for treating brain metastases from breast cancer.

Kodack DP, Askoxylakis V, Ferraro GB, Fukumura D, Jain RK.

Cancer Cell. 2015 Feb 9;27(2):163-75. doi: 10.1016/j.ccell.2015.01.001. Review.

43.

Quantum dot/antibody conjugates for in vivo cytometric imaging in mice.

Han HS, Niemeyer E, Huang Y, Kamoun WS, Martin JD, Bhaumik J, Chen Y, Roberge S, Cui J, Martin MR, Fukumura D, Jain RK, Bawendi MG, Duda DG.

Proc Natl Acad Sci U S A. 2015 Feb 3;112(5):1350-5. doi: 10.1073/pnas.1421632111. Epub 2015 Jan 20. Erratum in: Proc Natl Acad Sci U S A. 2015 Mar 3;112(9):E1048. Proc Natl Acad Sci U S A. 2015 Jun 9;112(23):E3087.

44.

Correlative intravital imaging of cGMP signals and vasodilation in mice.

Thunemann M, Schmidt K, de Wit C, Han X, Jain RK, Fukumura D, Feil R.

Front Physiol. 2014 Oct 14;5:394. doi: 10.3389/fphys.2014.00394. eCollection 2014.

45.

Magneto-fluorescent core-shell supernanoparticles.

Chen O, Riedemann L, Etoc F, Herrmann H, Coppey M, Barch M, Farrar CT, Zhao J, Bruns OT, Wei H, Guo P, Cui J, Jensen R, Chen Y, Harris DK, Cordero JM, Wang Z, Jasanoff A, Fukumura D, Reimer R, Dahan M, Jain RK, Bawendi MG.

Nat Commun. 2014 Oct 9;5:5093. doi: 10.1038/ncomms6093.

46.

Benefits of vascular normalization are dose and time dependent--letter.

Huang Y, Stylianopoulos T, Duda DG, Fukumura D, Jain RK.

Cancer Res. 2013 Dec 1;73(23):7144-6. doi: 10.1158/0008-5472.CAN-13-1989. Epub 2013 Nov 21. No abstract available.

47.

Effects of vascular-endothelial protein tyrosine phosphatase inhibition on breast cancer vasculature and metastatic progression.

Goel S, Gupta N, Walcott BP, Snuderl M, Kesler CT, Kirkpatrick ND, Heishi T, Huang Y, Martin JD, Ager E, Samuel R, Wang S, Yazbek J, Vakoc BJ, Peterson RT, Padera TP, Duda DG, Fukumura D, Jain RK.

J Natl Cancer Inst. 2013 Aug 21;105(16):1188-201. doi: 10.1093/jnci/djt164. Epub 2013 Jul 30. Erratum in: J Natl Cancer Inst. 2013 Nov 20;105(22):1762.

48.

Generation of functionally competent and durable engineered blood vessels from human induced pluripotent stem cells.

Samuel R, Daheron L, Liao S, Vardam T, Kamoun WS, Batista A, Buecker C, Schäfer R, Han X, Au P, Scadden DT, Duda DG, Fukumura D, Jain RK.

Proc Natl Acad Sci U S A. 2013 Jul 30;110(31):12774-9. doi: 10.1073/pnas.1310675110. Epub 2013 Jul 16. Erratum in: Proc Natl Acad Sci U S A. 2014 Feb 4;111(5):2047.

49.

Measuring interstitial diffusion, convection, and binding parameters in mouse tumors.

Jain RK, Munn LL, Fukumura D.

Cold Spring Harb Protoc. 2013 Jul 1;2013(7):678-80. doi: 10.1101/pdb.prot075721.

PMID:
23818670
50.

Measuring interstitial pH and pO2 in mouse tumors.

Jain RK, Munn LL, Fukumura D.

Cold Spring Harb Protoc. 2013 Jul 1;2013(7):675-7. doi: 10.1101/pdb.prot075713.

PMID:
23818669

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