DNA origami gets large: A double‐layer DNA‐origami tile with two orthogonal domains underwent self‐assembly into well‐ordered two‐dimensional DNA arrays with edge dimensions of 2–3 μm (see schematic representation and AFM image). This size is likely to be large enough to connect bottom‐up methods of patterning with top‐down approaches.

DNA nanotubes are cylinder-like structures formed from DNA double helical molecules whose helix axes are fused at least twice by crossovers. It is potentially useful to use such tubes as sheaths around rod-like species that arise in biological systems and in nanotechnology. It seems easiest to obtain such sheathing by joining two or more components around an object, rather than attempting to thread the object through a cavity in the tube. We report two examples of tubes containing a specific number of helices that are assembled from half-tube components. These tubes are a six-helix bundle and an eight-helix bundle, constructed respectively from a two bent triple crossover (BTX) molecules and from two 4-helix arched motifs. Both species contain single strands in one molecule that are missing in its mate. The six-helix bundle is formed from two different BTX molecules, whereas the 8-helix species is a closed cyclic dimer of the same molecule. We demonstrate the formation of these species by gel electrophoresis, and we examine their arrangement into long one-dimensional arrays by means of atomic force microscopy. KeywordsUnusual DNA motifs; DNA tubes; Curved motifs; Specific 1D DNA arrays; Molecular Sheaths DNA nanotubes have been produced in several laboratories. Many of these nanotubes are effectively combinations of DNA double crossover (DX) molecules, species that contain two DNA double helical domains that are linked to each other by two Holliday-like 1 crossover points; thus the two DNA double helices are fused by pairs of strands that cross over from one helix to another. 2 The two helix axes are coplanar, so that the unit can be thought of as a boxlike unit that may be tailed in sticky ends. DX molecules are known to be quite stiff, 3 and have found applications in forming periodic 4 and algorithmic 5 assemblies, in nanomechanical devices, 6 and in a translation system. 7 Two different types of DNA nanotubes have been reported: One type is formed from DX molecules tailed with sticky ends that associate with a non-planar angle between them, thereby producing the tube. 8,9 This type may be thought of as a two-dimensional array that has closed on itself, deliberately or otherwise, to form a (possibly skewed) cylindrical structure. Such tubes typically have a preferred size, but there is a certain amount of variation around this optimum. A second type of tube is designed to contain an exact number of helices, which is enforced on the molecule by sequence design. The bend angle between DX components is enforced by causing the strand switching between helices to occur at positions that lead to specific structures. For example, for DNA with 10.5 nucleotide pairs/turn, strand switching at separations of 7 or 14 nucleotides leads to 240° or 120° angles, resulting in a six-helix bundle. 10,11 A general method for producing low-stress DNA *Address correspondence to this author at ned.seeman@nyu.edu. # These authors have contributed equally to this work. Regardless of the general interest in designing cavities ...

Deep learning has been widely used for medical image segmentation and a large number of papers has been presented recording the success of deep learning in the field. A comprehensive thematic survey on medical image segmentation using deep learning techniques is presented. This paper makes two original contributions. Firstly, compared to traditional surveys that directly divide literatures of deep learning on medical image segmentation into many groups and introduce literatures in detail for each group, we classify currently popular literatures according to a multi‐level structure from coarse to fine. Secondly, this paper focuses on supervised and weakly supervised learning approaches, without including unsupervised approaches since they have been introduced in many old surveys and they are not popular currently. For supervised learning approaches, we analyse literatures in three aspects: the selection of backbone networks, the design of network blocks, and the improvement of loss functions. For weakly supervised learning approaches, we investigate literature according to data augmentation, transfer learning, and interactive segmentation, separately. Compared to existing surveys, this survey classifies the literatures very differently from before and is more convenient for readers to understand the relevant rationale and will guide them to think of appropriate improvements in medical image segmentation based on deep learning approaches.

Catenanes constructed from organic building blocks have been used in the demonstration of molecular devices such as positional switches, unidirectional motors, and other nanoscale functional materials. 1 In the nucleic acid world, catenanes have long been known; they are found in nature and are common in structural DNA nanotechnology. 2 Designed, all-DNA catenanes have been used as topological labels. 3 Crosslinks with organic linkages have been utilized to probe the structures and properties of DNA duplexes, hairpins, and higher order structures, such as t-RNA and ribozymes, 4 as well as to build DNA nanostructures and nanodevices. 5 In this paper, we describe the synthesis of a macrocycle that is prepared by formation of an amide linkage across one full turn of DNA, forming a tailed DNA/organic catenane containing 5'-and 3'-termini that are available for further functionalization.In prior work, we showed that 2'-pendent amines and carboxylates could be linked to form nylon along the phosphodiester backbone contour. 6 Our inquiry here began when we asked whether longer linkers could be used to attach polymeric components parallel to the helix axis. This target requires bridging approximately 35Å across a nucleic acid turn, which had not been reported previously (Fig. 1A), although there is now a report by Gothelf et al. 7 Tetraethylene glycol was used as a spacer into a carboxylate-functionalized uridine and undecaethylene glycol was incorporated into an aminefunctionalized uridine. The linker distances have not been optimized, although studies with tetraethylene glycol as spacer for both amine and caboxylate were unsuccessful.Three 16-mer ODNs 1, 2 and 3 were synthesized, where two modified uridines were separated by 8, 9 and 10 unmodified nucleotides, respectively. Cross-turn coupling using a DNA hairpin template gave > 97% yields of ODN 1 and 2, as estimated by MALDI-TOF spectra and denaturing gel electrophoresis, whereas the coupling yield of 3 was about 62 % (Table 1, Supporting Information). For further characterization, the coupled product was subjected to complete nuclease digestion followed by analysis to detect linked nucleotides. The detection of a polyethylene glycol (PEG)-amide linked uridine dimer by LCMS corroborated the formation of coupled products (Supporting Information).These data established the formula of the reaction product but did not distinguish between a newly formed linkage parallel to the helix axis (i.e., across the turn) versus along the phosphodiester backbone contour. However, templation of the reaction by a circular DNA template (Fig. 1A) would yield an interlocked complex only if the coupling reaction occurred across the turn. ODNs 1 and 2 paired with a 78-mer DNA circular template were subjected to E-mail: E-mail: james.canary@nyu.edu; E-mail: ned.seeman@nyu.edu. Supporting Information. Full experimental details including: Syntheses of phosphoramidites, MALDI-TOF MS of ODNs, LCMS analysis of complete nuclease digestion, denaturing gel analyses of catenane synthesis, exonucle...

Self-assembled DNA nanostructures have attracted significant research interest in biomedical applications because of their excellent programmability and biocompatibility. To develop multifunctional drug delivery from DNA nanostructures, considerable key information is still needed for clinical application. Traditional fixed endpoint assays do not reflect the dynamic and heterogeneous responses of cells with regard to drugs, and may lead to the misinterpretation of experimental results. For the first time, an integrated time-lapse live cell imaging system was used to study the cellular internalization and controlled drug release profile of three different shaped DNA origami/doxorubicin (DOX) complexes for three days. Our results demonstrated the dependence of DNA nanostructures on shape for drug delivery efficiency, while the rigid 3D DNA origami triangle frame exhibited enhanced cellular uptake capability, as compared with flexible 2D DNA structures. In addition, the translocation of released DOX into the nucleus was proved by fluorescence microscopy, in which a DOX-loaded 3D DNA triangle frame displayed a stronger accumulation of DOX in nuclei. Moreover, given the facile drug loading and auto fluorescence of the anti-cancer drug, DOX, our results suggest that the DNA nanostructure is a promising candidate, as a label-free nanocarrier, for DOX delivery, with great potential for anticancer therapy as well.

DNA‐Origami im großen Stil: Eine doppellagige DNA‐Origamikachel mit zwei orthogonalen Domänen bildete durch Selbstorganisation hoch reguläre 2D‐DNA‐Anordnungen mit Kantenlängen von 2–3 μm (siehe Schema und AFM‐Bild). Diese Größe dürfte vermutlich ausreichen, um Bottom‐up‐Methoden der Mustererzeugung mit Top‐down‐Ansätzen zu verknüpfen.

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