22,325 research outputs found
124-Color Super-resolution Imaging by Engineering DNA-PAINT Blinking Kinetics
Optical super-resolution techniques reach unprecedented spatial resolution down to a few nanometers. However, efficient multiplexing strategies for the simultaneous detection of hundreds of molecular species are still elusive. Here, we introduce an entirely new approach to multiplexed super-resolution microscopy by designing the blinking behavior of targets with engineered binding frequency and duration in DNA-PAINT. We assay this kinetic barcoding approach in silico and in vitro using DNA origami structures, show the applicability for multiplexed RNA and protein detection in cells, and finally experimentally demonstrate 124-plex super-resolution imaging within minutes.We thank Martin Spitaler and the imaging facility of the MPI of Biochemistry for confocal imaging support
Advanced superconducting magnets investigation
Mathematical models for steady state behavior of composite superconductors and experimental verification using magnet coi
The Geoff Egan Memorial Lecture 2011. Artefacts, art and artifice: reconsidering iconographic sources for archaeological objects in early modern Europe
A first systematic analysis of historic domestic material culture depicted in contemporaneous Western painting and prints, c.1400-1800. Drawing on an extensive data set, the paper proposes to methodologies and hermeneutics for historical analysis and archaeological correspondence
Continuations of the nonlinear Schr\"odinger equation beyond the singularity
We present four continuations of the critical nonlinear \schro equation (NLS)
beyond the singularity: 1) a sub-threshold power continuation, 2) a
shrinking-hole continuation for ring-type solutions, 3) a vanishing
nonlinear-damping continuation, and 4) a complex Ginzburg-Landau (CGL)
continuation. Using asymptotic analysis, we explicitly calculate the limiting
solutions beyond the singularity. These calculations show that for generic
initial data that leads to a loglog collapse, the sub-threshold power limit is
a Bourgain-Wang solution, both before and after the singularity, and the
vanishing nonlinear-damping and CGL limits are a loglog solution before the
singularity, and have an infinite-velocity{\rev{expanding core}} after the
singularity. Our results suggest that all NLS continuations share the universal
feature that after the singularity time , the phase of the singular core
is only determined up to multiplication by . As a result,
interactions between post-collapse beams (filaments) become chaotic. We also
show that when the continuation model leads to a point singularity and
preserves the NLS invariance under the transformation and
, the singular core of the weak solution is symmetric
with respect to . Therefore, the sub-threshold power and
the{\rev{shrinking}}-hole continuations are symmetric with respect to ,
but continuations which are based on perturbations of the NLS equation are
generically asymmetric
Testing the Hubble Law with the IRAS 1.2 Jy Redshift Survey
We test and reject the claim of Segal et al. (1993) that the correlation of
redshifts and flux densities in a complete sample of IRAS galaxies favors a
quadratic redshift-distance relation over the linear Hubble law. This is done,
in effect, by treating the entire galaxy luminosity function as derived from
the 60 micron 1.2 Jy IRAS redshift survey of Fisher et al. (1995) as a distance
indicator; equivalently, we compare the flux density distribution of galaxies
as a function of redshift with predictions under different redshift-distance
cosmologies, under the assumption of a universal luminosity function. This
method does not assume a uniform distribution of galaxies in space. We find
that this test has rather weak discriminatory power, as argued by Petrosian
(1993), and the differences between models are not as stark as one might expect
a priori. Even so, we find that the Hubble law is indeed more strongly
supported by the analysis than is the quadratic redshift-distance relation. We
identify a bias in the the Segal et al. determination of the luminosity
function, which could lead one to mistakenly favor the quadratic
redshift-distance law. We also present several complementary analyses of the
density field of the sample; the galaxy density field is found to be close to
homogeneous on large scales if the Hubble law is assumed, while this is not the
case with the quadratic redshift-distance relation.Comment: 27 pages Latex (w/figures), ApJ, in press. Uses AAS macros,
postscript also available at
http://www.astro.princeton.edu/~library/preprints/pop682.ps.g
Direct Visualization of Single Nuclear Pore Complex Proteins Using Genetically-Encoded Probes for DNA-PAINT
The nuclear pore complex (NPC) is one of the largest and most complex protein assemblies in the cell and, among other functions, serves as the gatekeeper of nucleocytoplasmic transport. Unraveling its molecular architecture and functioning has been an active research topic for decades with recent cryogenic electron microscopy and super-resolution studies advancing our understanding of the architecture of the NPC complex. However, the specific and direct visualization of single copies of NPC proteins is thus far elusive. Herein, we combine genetically-encoded self-labeling enzymes such as SNAP-tag and HaloTag with DNA-PAINT microscopy. We resolve single copies of nucleoporins in the human Y-complex in three dimensions with a precision of circa 3 nm, enabling studies of multicomponent complexes on the level of single proteins in cells using optical fluorescence microscopy
Discovery-led refinement in e-discovery investigations: sensemaking, cognitive ergonomics and system design.
Given the very large numbers of documents involved in e-discovery investigations, lawyers face a considerable challenge of collaborative sensemaking. We report findings from three workplace studies which looked at different aspects of how this challenge was met. From a sociotechnical perspective, the studies aimed to understand how investigators collectively and individually worked with information to support sensemaking and decision making. Here, we focus on discovery-led refinement; specifically, how engaging with the materials of the investigations led to discoveries that supported refinement of the problems and new strategies for addressing them. These refinements were essential for tractability. We begin with observations which show how new lines of enquiry were recursively embedded. We then analyse the conceptual structure of a line of enquiry and consider how reflecting this in e-discovery support systems might support scalability and group collaboration. We then focus on the individual activity of manual document review where refinement corresponded with the inductive identification of classes of irrelevant and relevant documents within a collection. Our observations point to the effects of priming on dealing with these efficiently and to issues of cognitive ergonomics at the humanâcomputer interface. We use these observations to introduce visualisations that might enable reviewers to deal with such refinements more efficiently
Integrated assessment of crop management portfolios in adapting to climate change in the Marchfeld region
Portfolio optimization is an adequate tool to find optimal crop management options in adapting to climate change. The risk farmers have to face can be caused by different sources. In our study, we focus on the risk arising from unknown weather conditions. Therefore, we developed stochastic climate change scenarios for the Marchfeld region. Two portfolio models have been applied in the time periods 2008-2020, 2021-2030 and 2031-2040: a traditional non-linear mean-variance (E-V) model and a model using the Conditional Value at Risk (CVaR) as risk metric. Investigated crops are corn, winter wheat, sunflower and spring barley with different crop management alternatives. Minimum tillage appears in all portfolios. We found a decreasing share of winter wheat that gets partially substituted by sunflower over the time periods. When including environmental constraints (soil organic carbon content, nitrate leaching) the reverse effect on the resulting portfolio shares is observed with corn being included. The E-V model reveals more diversification with respect to the crops, whereas the CVaR model shows more diversification with respect to crop management options
A Generalized Diffusion Tensor for Fully Anisotropic Diffusion of Energetic Particles in the Heliospheric Magnetic Field
The spatial diffusion of cosmic rays in turbulent magnetic fields can, in the
most general case, be fully anisotropic, i.e. one has to distinguish three
diffusion axes in a local, field-aligned frame. We reexamine the transformation
for the diffusion tensor from this local to a global frame, in which the Parker
transport equation for energetic particles is usually formulated and solved.
Particularly, we generalize the transformation formulas to allow for an
explicit choice of two principal local perpendicular diffusion axes. This
generalization includes the 'traditional' diffusion tensor in the special case
of isotropic perpendicular diffusion. For the local frame, we motivate the
choice of the Frenet-Serret trihedron which is related to the intrinsic
magnetic field geometry. We directly compare the old and the new tensor
elements for two heliospheric magnetic field configurations, namely the hybrid
Fisk and the Parker field. Subsequently, we examine the significance of the
different formulations for the diffusion tensor in a standard 3D model for the
modulation of galactic protons. For this we utilize a numerical code to
evaluate a system of stochastic differential equations equivalent to the Parker
transport equation and present the resulting modulated spectra. The computed
differential fluxes based on the new tensor formulation deviate from those
obtained with the 'traditional' one (only valid for isotropic perpendicular
diffusion) by up to 60% for energies below a few hundred MeV depending on
heliocentric distance.Comment: 8 pages, 6 figures, accepted in Ap
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