Engineering DNA quadruplexes in DNA nanostructures for biosensor construction

DNA quadruplexes are nucleic acid conformations comprised of four strands.They are prevalent in human genomes and increasing efforts are being directed toward t...     

Plant functional modelling as a basis for assessing the impact of management on plant safety

A major objective of the present work is to provide means for representing a chemical process plant as a socio-technical system, so as to allow hazard identification at a high level in order to identify major targets for safety development. The main phases of the methodology are: (1) preparation of a plant functional model where a set of plant functions describes coherently hardware, software, operations, work organization and other safety related aspects. The basic principle is that any aspect of the plant can be represented by an object based upon an Intent and associated with each Intent are Methods, by which the Intent is realized, and Constraints, which limit the Intent. (2) Plant level hazard identification based on keywords/checklists and the functional model. (3) Development of incident scenarios and selection of hazardous situation with different safety characteristics. (4) Evaluation of the impact of management on plant safety through interviews. (5) Identification of safety critical ways of action in the management system, i.e. identification of possible error- and violation-producing conditions.     

Acceptable risk as a basis for design

Historically, human civilisations have striven to protect themselves against natural and man-made hazards. The degree of protection is a matter of political choice. Today this choice should be expressed in terms of risk and acceptable probability of failure to form the basis of the probabilistic design of the protection. It is additionally argued that the choice for a certain technology and the connected risk is made in a cost-benefit framework. The benefits and the costs including risk are weighed in the decision process. A set of rules for the evaluation of risk is proposed and tested in cases. The set of rules leads to technical advice in a question that has to be decided politically.     

Self-assembled DNA nanostructures for distance-dependent multivalent ligand-protein binding

An important goal of nanotechnology is to assemble multiple molecules while controlling the spacing between them. Of particular interest is the phenomenon of multivalency, which is characterized by simultaneous binding of multiple ligands on one biological entity to multiple receptors on another. Various approaches have been developed to engineer multivalency by linking multiple ligands together. However, the effects of well-controlled inter-ligand distances on multivalency are less well understood. Recent progress in self-assembling DNA nanostructures with spatial and sequence addressability has made deterministic positioning of different molecular species possible. Here we show that distance-dependent multivalent binding effects can be systematically investigated by incorporating multiple-affinity ligands into DNA nanostructures with precise nanometre spatial control. Using atomic force microscopy, we demonstrate direct visualization of high-affinity bivalent ligands being used as pincers to capture and display protein molecules on a nanoarray. These results illustrate the potential of using designer DNA nanoscaffolds to engineer more complex and interactive biomolecular networks.     

Structural basis for near unity quantum yield core/shell nanostructures

Aberration-corrected Z-contrast scanning transmission electron microscopy of core/shell nanocrystals shows clear correlations between structure and quantum efficiency. Uniform shell coverage is obtained only for a graded CdS/ZnS shell material and is found to be critical to achieving near 100% quantum yield. The sublattice sensitivity of the images confirms that preferential growth takes place on the anion-terminated surfaces. This explains the three-dimensional "nanobullet" shape observed in the case of core/shell nanorods.     

Building plasmonic nanostructures with DNA

Plasmonic structures can be constructed from precise numbers of well-defined metal nanoparticles that are held together with molecular linkers, templates or spacers. Such structures could be used to concentrate, guide and switch light on the nanoscale in sensors and various other devices. DNA was first used to rationally design plasmonic structures in 1996, and more sophisticated motifs have since emerged as effective and versatile species for guiding the assembly of plasmonic nanoparticles into structures with useful properties. Here we review the design principles for plasmonic nanostructures, and discuss how DNA has been applied to build finite-number assemblies (plasmonic molecules), regularly spaced nanoparticle chains (plasmonic polymers) and extended two- and three-dimensional ordered arrays (plasmonic crystals).     

Patient-specific simulation as a basis for clinical decision-making

Patient-specific medical simulation holds the promise of determining tailored medical treatment based on the characteristics of an individual patient (for example, using a genotypic assay of a sequence of DNA). Decision-support systems based on patient-specific simulation can potentially revolutionize the way that clinicians plan courses of treatment for various conditions, ranging from viral infections to arterial abnormalities. Basing medical decisions on the results of simulations that use models derived from data specific to the patient in question means that the effectiveness of a range of potential treatments can be assessed before they are actually administered, preventing the patient from experiencing unnecessary or ineffective treatments. We illustrate the potential for patient-specific simulation by first discussing the scale of the evolving international grid infrastructure that is now available to underpin such applications. We then consider two case studies, one concerned with the treatment of patients with HIV/AIDS and the other addressing neuropathologies associated with the intracranial vasculature. Such patient-specific medical simulations require access to both appropriate patient data and the computational resources on which to perform potentially very large simulations. Computational infrastructure providers need to furnish access to a wide range of different types of resource, typically made available through heterogeneous computational grids, and to institute policies that facilitate the performance of patient-specific simulations on those resources. To support these kinds of simulations, where life and death decisions are being made, computational resource providers must give urgent priority to such jobs, for example by allowing them to pre-empt the queue on a machine and run straight away. We describe systems that enable such priority computing.     

Covalent tethering of protruding arms for addressable DNA nanostructures

Functionalization of self-assembled DNA nanostructures is of fundamental importance for the realization of their application in nanotechnology and biosensing. Approaches reported so far suffer from lack of general applicability and usually require careful system design to avoid poor yields in the assembly of target structures. A novel approach well suited for fabrication of addressable DNA superstructures is reported here to generate DNA tile motifs. The method is based on the covalent linkage of a single-stranded protruding arm (covPA) to one of the oligomers forming the tile. Subsequent to assembly of tile motifs and superlattices, the covPA can be addressed by hybridization with complementary oligonucleotides or DNA-protein conjugates. The covPA can be located at arbitrary positions in a given tile motif without changing the general design and without compromising the structural integrity of the tile. The covPA strategy can also be readily extended to different PA sequences and multiple covPA arms can be linked to a tile. Superlattices obtained by self-assembly of covPA tiles reveal partial folding into double layers which possess an intrinsic order at the ultrastructural level. This phenomenon is likely associated with the increased flexibility of the covPA and might open up novel ways for DNA-based functionalization of solid surfaces and other applications of structural DNA nanotechnology.     

Orthogonal protein decoration of DNA nanostructures

The development of robust DNA-protein coupling techniques is mandatory for applications of DNA nanostructures in biomedical diagnostics, fundamental biochemistry, and other fields in biomolecular nanosciences. The use of self-labeling fusion proteins, which are orthogonal to biotin-streptavidin and antibody-antigen interactions, is described for the site-selective protein decoration of two exemplary DNA nanostructures: a four-way junction X-tile motif and a 3D DNA tetrahedron. Multifunctional DNA superstructures bearing up to four different proteins are generated and characterized by electrophoresis and microplate-based functionality assays. Steric and electrostatic interactions are identified as critical parameters controlling the efficiency of DNA-protein ligation. The results indicate that this method is versatile and broadly applicable, not only for the functionalization of DNA architectures but also for the site-specific decoration of other molecular materials and devices containing several different proteins.     

Operating load as a basis for evaluating fatigue endurance

Conclutions A knowledge of operating-load variation is very important for optimum evaluation of structural dimensions. A decisive factor in the choice of method is primarily the designer's experience, but apparatus and experimental equipment in the design laboratory play an important role. From the viewpoint of evaluation and checking machine part endurance the rain runoff method assumes considerable importance since it reflects modern ideas about material fracture better than other methods. However, use of this method requires modern computer techniques.Translated from Problemy Prochnosti, No. 9, pp. 34–40, September, 1980.     

Self-assembly of functional nanostructures from ABC triblock copolymers

The spontaneous formation of nanostructured materials by molecular self-assembly of block copolymers is an active area of research, driven both by its inherent beauty and by a wealth of potential technological applications. Thin films of block copolymers have attracted increasing interest, particularly in view of possible applications in nanotechnology. Although much of the work has concentrated on block copolymers consisting of two components, the insertion of a third block greatly enlarges the structural diversity and allows incorporation of additional chemical functionality. Here we describe a highly ordered hexagonally perforated lamella structure based on an ABC triblock copolymer thin film. By suitable choice of the three blocks a versatile structure is formed. The perforated lamella can serve as a lithographic mask, it can be chemically converted into an amphiphilic structure without losing its order, and after selective removal of one of its constituents it could be used as a responsive membrane. Intriguingly, the particular choice of the blocks ensures that the structure is formed irrespective of the chemical nature of the solid substrate. The experimental results are supported by mesoscale computer simulations.     

Reconfigurable, braced, three-dimensional DNA nanostructures

DNA nanotechnology makes use of the exquisite self-recognition of DNA in order to build on a molecular scale. Although static structures may find applications in structural biology and computer science, many applications in nanomedicine and nanorobotics require the additional capacity for controlled three-dimensional movement. DNA architectures can span three dimensions and DNA devices are capable of movement, but active control of well-defined three-dimensional structures has not been achieved. We demonstrate the operation of reconfigurable DNA tetrahedra whose shapes change precisely and reversibly in response to specific molecular signals. Shape changes are confirmed by gel electrophoresis and by bulk and single-molecule F?rster resonance energy transfer measurements. DNA tetrahedra are natural building blocks for three-dimensional construction; they may be synthesized rapidly with high yield of a single stereoisomer, and their triangulated architecture conveys structural stability. The introduction of shape-changing structural modules opens new avenues for the manipulation of matter on the nanometre scale.     

One-dimensional ZnO nanostructures: Solution growth and functional properties

One-dimensional (1D) ZnO nanostructures have been studied intensively and extensively over the last decade not only for their remarkable chemical and physical properties, but also for their current and future diverse technological applications. This article gives a comprehensive overview of the progress that has been made within the context of 1D ZnO nanostructures synthesized via wet chemical methods. We will cover the synthetic methodologies and corresponding growth mechanisms, different structures, doping and alloying, position-controlled growth on substrates, and finally, their functional properties as catalysts, hydrophobic surfaces, sensors, and in nanoelectronic, optical, optoelectronic, and energy harvesting devices.      

Folding and cutting DNA into reconfigurable topological nanostructures

Topology is the mathematical study of the spatial properties that are preserved through the deformation, twisting and stretching of objects. Topological architectures are common in nature and can be seen, for example, in DNA molecules that condense and relax during cellular events. Synthetic topological nanostructures, such as catenanes and rotaxanes, have been engineered using supramolecular chemistry, but the fabrication of complex and reconfigurable structures remains challenging. Here, we show that DNA origami can be used to assemble a M?bius strip, a topological ribbon-like structure that has only one side. In addition, we show that the DNA M?bius strip can be reconfigured through strand displacement to create topological objects such as supercoiled ring and catenane structures. This DNA fold-and-cut strategy, analogous to Japanese kirigami, may be used to create and reconfigure programmable topological structures that are unprecedented in molecular engineering.     

Radial basis functional model for multi-objective sheet metal forming optimization

Fracture and wrinkling are two major defects in sheet metal forming and can be eliminated via an appropriate drawbead design. This article proposes to adopt a multi-objective particle swarm optimization (MOPSO) approach, which differs from traditional multi-objective optimization with construction of a single cost function. MOPSO shows a certain advantage over other single cost function or population-based algorithms. While radial basis function (RBF) has shown considerable promise in highly non-linear problems, there has been no report in sheet metal forming design. Here RBF is attempted to establish the metamodels for fracture and wrinkling criteria in sheet metal forming design. In this article, a sophisticated automobile inner stamping case is exemplified, which demonstrated that RBF provides a better surrogate accuracy and MOPSO is more effective than the other methods studied. The use of RBF driven MOPSO procedure significantly improved the formability and can be recommended for sheet metal process design.     

Hydrogen-bonded nanotubes as a model for DNA transcription

Using the energy asymmetries in the hydrogen-bonded structures, the model is formulated explaining melting of DNA double chain and also explaining further decay of only one of the obtained single chains. The model is similar to the Scott's model of alpha-helix, where the spiral is substituted with interacting discs. The explanation of mentioned DNA transformation is based on the estimate of free energy of discs with an even number of hydrogen bonds, and an estimate of melting point temperature for the subsystem of odd index fibers and transition temperature of the subsystem of even index fibers.