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 $T_c$, the phase of the singular core is only determined up to multiplication by $e^{i\theta}$. 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 $t\rightarrow-t$ and $\psi\rightarrow\psi^\ast$, the singular core of the weak solution is symmetric with respect to $T_c$. Therefore, the sub-threshold power and the{\rev{shrinking}}-hole continuations are symmetric with respect to $T_c$, 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 human–computer 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