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  • 1
    Publication Date: 2009-05-22
    Description: Molecular self-assembly offers a 'bottom-up' route to fabrication with subnanometre precision of complex structures from simple components. DNA has proved to be a versatile building block for programmable construction of such objects, including two-dimensional crystals, nanotubes, and three-dimensional wireframe nanopolyhedra. Templated self-assembly of DNA into custom two-dimensional shapes on the megadalton scale has been demonstrated previously with a multiple-kilobase 'scaffold strand' that is folded into a flat array of antiparallel helices by interactions with hundreds of oligonucleotide 'staple strands'. Here we extend this method to building custom three-dimensional shapes formed as pleated layers of helices constrained to a honeycomb lattice. We demonstrate the design and assembly of nanostructures approximating six shapes-monolith, square nut, railed bridge, genie bottle, stacked cross, slotted cross-with precisely controlled dimensions ranging from 10 to 100 nm. We also show hierarchical assembly of structures such as homomultimeric linear tracks and heterotrimeric wireframe icosahedra. Proper assembly requires week-long folding times and calibrated monovalent and divalent cation concentrations. We anticipate that our strategy for self-assembling custom three-dimensional shapes will provide a general route to the manufacture of sophisticated devices bearing features on the nanometre scale.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2688462/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2688462/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Douglas, Shawn M -- Dietz, Hendrik -- Liedl, Tim -- Hogberg, Bjorn -- Graf, Franziska -- Shih, William M -- 1DP2OD004641-01/OD/NIH HHS/ -- DP2 OD004641/OD/NIH HHS/ -- DP2 OD004641-01/OD/NIH HHS/ -- England -- Nature. 2009 May 21;459(7245):414-8. doi: 10.1038/nature08016.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19458720" target="_blank"〉PubMed〈/a〉
    Keywords: DNA/*chemistry/ultrastructure ; Microscopy, Electron, Transmission ; Nanostructures/*chemistry/ultrastructure ; Nanotechnology/*methods ; *Nucleic Acid Conformation
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2012-02-22
    Description: We describe an autonomous DNA nanorobot capable of transporting molecular payloads to cells, sensing cell surface inputs for conditional, triggered activation, and reconfiguring its structure for payload delivery. The device can be loaded with a variety of materials in a highly organized fashion and is controlled by an aptamer-encoded logic gate, enabling it to respond to a wide array of cues. We implemented several different logical AND gates and demonstrate their efficacy in selective regulation of nanorobot function. As a proof of principle, nanorobots loaded with combinations of antibody fragments were used in two different types of cell-signaling stimulation in tissue culture. Our prototype could inspire new designs with different selectivities and biologically active payloads for cell-targeting tasks.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Douglas, Shawn M -- Bachelet, Ido -- Church, George M -- New York, N.Y. -- Science. 2012 Feb 17;335(6070):831-4. doi: 10.1126/science.1214081.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wyss Institute for Biologically Inspired Engineering, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22344439" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD/immunology ; Antigens, Differentiation, Myelomonocytic/immunology ; Cell Line, Tumor ; *DNA/chemistry ; Histocompatibility Antigens Class I/immunology ; Humans ; Immunoglobulin Fragments/immunology ; Metal Nanoparticles ; Mice ; Molecular Conformation ; *Nanostructures ; *Robotics ; Sialic Acid Binding Ig-like Lectin 3 ; *Signal Transduction
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-08-08
    Description: We demonstrate the ability to engineer complex shapes that twist and curve at the nanoscale from DNA. Through programmable self-assembly, strands of DNA are directed to form a custom-shaped bundle of tightly cross-linked double helices, arrayed in parallel to their helical axes. Targeted insertions and deletions of base pairs cause the DNA bundles to develop twist of either handedness or to curve. The degree of curvature could be quantitatively controlled, and a radius of curvature as tight as 6 nanometers was achieved. We also combined multiple curved elements to build several different types of intricate nanostructures, such as a wireframe beach ball or square-toothed gears.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2737683/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2737683/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dietz, Hendrik -- Douglas, Shawn M -- Shih, William M -- 1DP2OD004641-01/OD/NIH HHS/ -- DP2 OD004641/OD/NIH HHS/ -- DP2 OD004641-01/OD/NIH HHS/ -- New York, N.Y. -- Science. 2009 Aug 7;325(5941):725-30. doi: 10.1126/science.1174251.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19661424" target="_blank"〉PubMed〈/a〉
    Keywords: Base Pairing ; DNA/*chemistry/ultrastructure ; *Nanostructures ; Nanotechnology ; *Nucleic Acid Conformation
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2017-02-25
    Description: A central question in conservation is how best to manage biodiversity, despite human domination of global processes (= Anthropocene). Common responses (i.e. translocations, genetic rescue) forestall potential extirpations, yet have an uncertain duration. A textbook example is the greater prairie chicken (GRPC: Tympanuchus cupido pinnatus ), where translocations (1992–1998) seemingly rescued genetically depauperate Illinois populations. We re-evaluated this situation after two decades by genotyping 21 microsatellite loci from 1831 shed feathers across six leks in two counties over 4 years (2010–2013). Low migration rates (less than 1%) established each county as demographically independent, but with declining-population estimates (4 year average N = 79). Leks were genetically similar and significantly bottlenecked, with low effective population sizes (average N e = 13.1; 4 year N e / N = 0.166). Genetic structure was defined by 12 significantly different family groups, with relatedness r = 0.31 〉 half-sib r = 0.25. Average heterozygosity, indicating short-term survival, did not differ among contemporary, pre- and post-translocated populations, whereas allelic diversity did. Our results, the natural history of GRPC (i.e. few leks, male dominance hierarchies) and its controlled immigration suggest demographic expansion rather than genetic rescue. Legal protection under the endangered species act (ESA) may enhance recovery, but could exacerbate political–economic concerns on how best to manage ‘conservation-reliant’ species, for which GRPC is now an exemplar.
    Keywords: genetics, ecology, evolution
    Electronic ISSN: 2054-5703
    Topics: Natural Sciences in General
    Published by Royal Society
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  • 5
    Publication Date: 2016-06-21
    Description: Scalable production of DNA nanostructures remains a substantial obstacle to realizing new applications of DNA nanotechnology. Typical DNA nanostructures comprise hundreds of DNA oligonucleotide strands, where each unique strand requires a separate synthesis step. New design methods that reduce the strand count for a given shape while maintaining overall size and complexity would be highly beneficial for efficiently producing DNA nanostructures. Here, we report a method for folding a custom template strand by binding individual staple sequences to multiple locations on the template. We built several nanostructures for well-controlled testing of various design rules, and demonstrate folding of a 6-kb template by as few as 10 unique strand sequences binding to 10 ± 2 locations on the template strand.
    Keywords: Nucleic acid structure, Phsyical and Biochemical Characterisation of DNA
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 6
    Publication Date: 2012-07-25
    Description: Rapid advances in DNA sequencing promise to enable new diagnostics and individualized therapies. Achieving personalized medicine, however, will require extensive research on highly reidentifiable, integrated datasets of genomic and health information. To assist with this, participants in the Personal Genome Project choose to forgo privacy via our institutional review board- approved “open consent” process. The contribution of public data and samples facilitates both scientific discovery and standardization of methods. We present our findings after enrollment of more than 1,800 participants, including whole-genome sequencing of 10 pilot participant genomes (the PGP-10). We introduce the Genome-Environment-Trait Evidence (GET-Evidence) system. This tool automatically processes genomes and prioritizes both published and novel variants for interpretation. In the process of reviewing the presumed healthy PGP-10 genomes, we find numerous literature references implying serious disease. Although it is sometimes impossible to rule out a late-onset effect, stringent evidence requirements can address the high rate of incidental findings. To that end we develop a peer production system for recording and organizing variant evaluations according to standard evidence guidelines, creating a public forum for reaching consensus on interpretation of clinically relevant variants. Genome analysis becomes a two-step process: using a prioritized list to record variant evaluations, then automatically sorting reviewed variants using these annotations. Genome data, health and trait information, participant samples, and variant interpretations are all shared in the public domain—we invite others to review our results using our participant samples and contribute to our interpretations. We offer our public resource and methods to further personalized medical research.
    Keywords: Inaugural Articles
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 7
    Publication Date: 2012-05-31
    Description: We test the utility of the OII 83.4 nm emission feature as a measure of ionospheric parameters. Observed with the Remote Atmospheric and Ionospheric Detection System (RAIDS) Extreme Ultraviolet Spectrograph on the International Space Station (ISS), limb profiles of 83.4 nm emissions are compared to predicted dayglow emission profiles from a theoretical model incorporating ground-based electron density profiles measured by the Millstone Hill radar and parameterized by a best-fit Chapman-α function. Observations and models are compared for periods of conjunction between Millstone Hill and the RAIDS fields-of-view. These RAIDS observations show distinct differences in topside morphology between two days, 15 January and 10 March 2010, closely matching the forward model morphology and demonstrating that 83.4 nm emission is sensitive to changes in the ionospheric density profile from the 340 km altitude of the ISS during solar minimum. We find no significant difference between 83.4 nm emission profiles modeled assuming a constant scale height Chapman-α best-fit to the ISR measurements and those assuming varying scale height.
    Print ISSN: 0148-0227
    Topics: Geosciences , Physics
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 8
    Publication Date: 2007-04-02
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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