18,125 research outputs found
Art/Sci Nexus, 9 Evenings Revisited
Following the exhibition of Hybrid Bodies at KKW in 2016 Andrew Carnie and I were invited back to act as mentors to a group of young artists and scientists from all over Europe undertaking a week long workshop designed to lead to new art/science collaborations. We were also invited to present the Hybrid Bodies project at a one day public event preceding the workshop
Massively parallel single-molecule manipulation using centrifugal force
Precise manipulation of single molecules has already led to remarkable
insights in physics, chemistry, biology and medicine. However, widespread
adoption of single-molecule techniques has been impeded by equipment cost and
the laborious nature of making measurements one molecule at a time. We have
solved these issues with a new approach: massively parallel single-molecule
force measurements using centrifugal force. This approach is realized in a
novel instrument that we call the Centrifuge Force Microscope (CFM), in which
objects in an orbiting sample are subjected to a calibration-free,
macroscopically uniform force-field while their micro-to-nanoscopic motions are
observed. We demonstrate high-throughput single-molecule force spectroscopy
with this technique by performing thousands of rupture experiments in parallel,
characterizing force-dependent unbinding kinetics of an antibody-antigen pair
in minutes rather than days. Additionally, we verify the force accuracy of the
instrument by measuring the well-established DNA overstretching transition at
66 3 pN. With significant benefits in efficiency, cost, simplicity, and
versatility, "single-molecule centrifugation" has the potential to
revolutionize single-molecule experimentation, and open access to a wider range
of researchers and experimental systems.Comment: 5 pages, 3 figure
Catalyzed relaxation of a metastable DNA fuel
Practically all of life's molecular processes, from chemical synthesis to replication, involve enzymes that carry out their functions through
the catalytic transformation of metastable fuels into waste products.
Catalytic control of reaction rates will prove to be as useful and
ubiquitous in nucleic-acid-based engineering as it is in biology. Here
we report a metastable DNA "fuel" and a corresponding DNA
"catalyst" that improve upon the original hybridization-based
catalyst system (Turberfield et al. Phys. Rev. Lett. 90,
118102-1118102-4) by more than 2 orders of magnitude. This is achieved
by identifying and purifying a fuel with a kinetically trapped
metastable configuration consisting of a "kissing loop" stabilized
by flanking helical domains; the catalyst strand acts by opening a
helical domain and allowing the complex to relax to its ground state by
a multistep pathway. The improved fuel/catalyst system shows a roughly
5000-fold acceleration of the uncatalyzed reaction, with each catalyst
molecule capable of turning over in excess of 40 substrates. With
k_(cat)/K_M ≈ 10^7/M/min, comparable to many protein
enzymes and ribozymes, this fuel system becomes a viable component
enabling future DNA-based synthetic molecular machines and logic
circuits. As an example, we designed and characterized a signal
amplifier based on the fuel-catalyst system. The amplifier uses a
single strand of DNA as input and releases a second strand with
unrelated sequence as output. A single input strand can catalytically
trigger the release of more than 10 output strands
Hydraulic fracturing in cells and tissues: fracking meets cell biology
The animal body is fundamentally made of water. A small fraction of this water is freely flowing in blood and lymph, but most of it is trapped in hydrogels such as the extracellular matrix (ECM), the cytoskeleton, and chromatin. Besides providing a medium for biological molecules to diffuse, water trapped in hydrogels plays a fundamental mechanical role. This role is well captured by the theory of poroelasticity, which explains how any deformation applied to a hydrogel causes pressure gradients and water flows, much like compressing a sponge squeezes water out of it. Here we review recent evidence that poroelastic pressures and flows can fracture essential biological barriers such as the nuclear envelope, the cellular cortex, and epithelial layers. This type of fracture is known in engineering literature as hydraulic fracturing or "fracking"Peer ReviewedPostprint (author's final draft
Microsystems technology: objectives
This contribution focuses on the objectives of microsystems technology (MST). The reason for this is two fold. First of all, it should explain what MST actually is. This question is often posed and a simple answer is lacking, as a consequence of the diversity of subjects that are perceived as MST. The second reason is that a map of the somewhat chaotic field of MST is needed to identify sub-territories, for which standardization in terms of system modules an interconnections is feasible. To define the objectives a pragmatic approach has been followed. From the literature a selection of topics has been chosen and collected that are perceived as belonging to the field of MST by a large community of workers in the field (more than 250 references). In this way an overview has been created with `applications¿ and `generic issues¿ as the main characteristics
Millimeter-wave radiometry for radio astronomy Final report
Lunation study using millimeter wave radiometry for radio astronom
Challenging the Computational Metaphor: Implications for How We Think
This paper explores the role of the traditional computational metaphor in our thinking as computer scientists, its influence on epistemological styles, and its implications for our understanding of cognition. It proposes to replace the conventional metaphor--a sequence of steps--with the notion of a community of interacting entities, and examines the ramifications of such a shift on these various ways in which we think
High-Density Genotypes of Inbred Mouse Strains: Improved Power and Precision of Association Mapping.
Human genome-wide association studies have identified thousands of loci associated with disease phenotypes. Genome-wide association studies also have become feasible using rodent models and these have some important advantages over human studies, including controlled environment, access to tissues for molecular profiling, reproducible genotypes, and a wide array of techniques for experimental validation. Association mapping with common mouse inbred strains generally requires 100 or more strains to achieve sufficient power and mapping resolution; in contrast, sample sizes for human studies typically are one or more orders of magnitude greater than this. To enable well-powered studies in mice, we have generated high-density genotypes for ∼175 inbred strains of mice using the Mouse Diversity Array. These new data increase marker density by 1.9-fold, have reduced missing data rates, and provide more accurate identification of heterozygous regions compared with previous genotype data. We report the discovery of new loci from previously reported association mapping studies using the new genotype data. The data are freely available for download, and Web-based tools provide easy access for association mapping and viewing of the underlying intensity data for individual loci
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