1,284 research outputs found
Tverberg's Theorem at 50: Extensions and Counterexamples
We describe how a powerful new “constraint
method” yields many different extensions of the topological
version of Tverberg’s 1966 Theorem in the prime power case—
and how the same method also was instrumental in the recent
spectacular construction of counterexamples for the general
case
On a new conformal functional for simplicial surfaces
We introduce a smooth quadratic conformal functional and its weighted version
where
is the extrinsic intersection angle of the circumcircles of the
triangles of the mesh sharing the edge and is the valence of
vertex . Besides minimizing the squared local conformal discrete Willmore
energy this functional also minimizes local differences of the angles
. We investigate the minimizers of this functionals for simplicial
spheres and simplicial surfaces of nontrivial topology. Several remarkable
facts are observed. In particular for most of randomly generated simplicial
polyhedra the minimizers of and are inscribed polyhedra. We
demonstrate also some applications in geometry processing, for example, a
conformal deformation of surfaces to the round sphere. A partial theoretical
explanation through quadratic optimization theory of some observed phenomena is
presented.Comment: 14 pages, 8 figures, to appear in the proceedings of "Curves and
Surfaces, 8th International Conference", June 201
Realizability of Polytopes as a Low Rank Matrix Completion Problem
This article gives necessary and sufficient conditions for a relation to be
the containment relation between the facets and vertices of a polytope. Also
given here, are a set of matrices parameterizing the linear moduli space and
another set parameterizing the projective moduli space of a combinatorial
polytope
GPs' willingness to prescribe aspirin for cancer preventive therapy in Lynch syndrome: a factorial randomised trial investigating factors influencing decisions.
BACKGROUND: The National Institute for Health and Care Excellence (NICE) 2020 guidelines recommends aspirin for colorectal cancer prevention for people with Lynch syndrome. Strategies to change practice should be informed by understanding the factors influencing prescribing. AIM: To investigate the optimal type and level of information to communicate with GPs to increase willingness to prescribe aspirin. DESIGN AND SETTING: GPs in England and Wales (n = 672) were recruited to participate in an online survey with a 23 factorial design. GPs were randomised to one of eight vignettes describing a hypothetical patient with Lynch syndrome recommended to take aspirin by a clinical geneticist. METHOD: Across the vignettes, the presence or absence of three types of information was manipulated: 1) existence of NICE guidance; 2) results from the CAPP2 trial; 3) information comparing risks/benefits of aspirin. The main effects and all interactions on the primary (willingness to prescribe) and secondary outcomes (comfort discussing aspirin) were estimated. RESULTS: There were no statistically significant main effects or interactions of the three information components on willingness to prescribe aspirin or comfort discussing harms and benefits. In total, 80.4% (540/672) of GPs were willing to prescribe, with 19.7% (132/672) unwilling. GPs with prior awareness of aspirin for preventive therapy were more comfortable discussing the medication than those unaware (P = 0.031). CONCLUSION: It is unlikely that providing information on clinical guidance, trial results, and information comparing benefits and harms will increase aspirin prescribing for Lynch syndrome in primary care. Alternative multilevel strategies to support informed prescribing may be warranted
How much contextuality?
The amount of contextuality is quantified in terms of the probability of the
necessary violations of noncontextual assignments to counterfactual elements of
physical reality.Comment: 5 pages, 3 figure
Parameter Estimation and Quantitative Parametric Linkage Analysis with GENEHUNTER-QMOD
Objective: We present a parametric method for linkage analysis of quantitative phenotypes. The method provides a test for linkage as well as an estimate of different phenotype parameters. We have implemented our new method in the program GENEHUNTER-QMOD and evaluated its properties by performing simulations. Methods: The phenotype is modeled as a normally distributed variable, with a separate distribution for each genotype. Parameter estimates are obtained by maximizing the LOD score over the normal distribution parameters with a gradient-based optimization called PGRAD method. Results: The PGRAD method has lower power to detect linkage than the variance components analysis (VCA) in case of a normal distribution and small pedigrees. However, it outperforms the VCA and Haseman-Elston regression for extended pedigrees, nonrandomly ascertained data and non-normally distributed phenotypes. Here, the higher power even goes along with conservativeness, while the VCA has an inflated type I error. Parameter estimation tends to underestimate residual variances but performs better for expectation values of the phenotype distributions. Conclusion: With GENEHUNTER-QMOD, a powerful new tool is provided to explicitly model quantitative phenotypes in the context of linkage analysis. It is freely available at http://www.helmholtz-muenchen.de/genepi/downloads. Copyright (C) 2012 S. Karger AG, Base
Virtual screening for inhibitors of the human TSLP:TSLPR interaction
The pro-inflammatory cytokine thymic stromal lymphopoietin (TSLP) plays a pivotal role in the pathophysiology of various allergy disorders that are mediated by type 2 helper T cell (Th2) responses, such as asthma and atopic dermatitis. TSLP forms a ternary complex with the TSLP receptor (TSLPR) and the interleukin-7-receptor subunit alpha (IL-7Ra), thereby activating a signaling cascade that culminates in the release of pro-inflammatory mediators. In this study, we conducted an in silico characterization of the TSLP: TSLPR complex to investigate the drugability of this complex. Two commercially available fragment libraries were screened computationally for possible inhibitors and a selection of fragments was subsequently tested in vitro. The screening setup consisted of two orthogonal assays measuring TSLP binding to TSLPR: a BLI-based assay and a biochemical assay based on a TSLP: alkaline phosphatase fusion protein. Four fragments pertaining to diverse chemical classes were identified to reduce TSLP: TSLPR complex formation to less than 75% in millimolar concentrations. We have used unbiased molecular dynamics simulations to develop a Markov state model that characterized the binding pathway of the most interesting compound. This work provides a proof-ofprinciple for use of fragments in the inhibition of TSLP: TSLPR complexation
Computing the vertices of tropical polyhedra using directed hypergraphs
We establish a characterization of the vertices of a tropical polyhedron
defined as the intersection of finitely many half-spaces. We show that a point
is a vertex if, and only if, a directed hypergraph, constructed from the
subdifferentials of the active constraints at this point, admits a unique
strongly connected component that is maximal with respect to the reachability
relation (all the other strongly connected components have access to it). This
property can be checked in almost linear-time. This allows us to develop a
tropical analogue of the classical double description method, which computes a
minimal internal representation (in terms of vertices) of a polyhedron defined
externally (by half-spaces or hyperplanes). We provide theoretical worst case
complexity bounds and report extensive experimental tests performed using the
library TPLib, showing that this method outperforms the other existing
approaches.Comment: 29 pages (A4), 10 figures, 1 table; v2: Improved algorithm in section
5 (using directed hypergraphs), detailed appendix; v3: major revision of the
article (adding tropical hyperplanes, alternative method by arrangements,
etc); v4: minor revisio
Observation of Electron-Hole Puddles in Graphene Using a Scanning Single Electron Transistor
The electronic density of states of graphene is equivalent to that of
relativistic electrons. In the absence of disorder or external doping the Fermi
energy lies at the Dirac point where the density of states vanishes. Although
transport measurements at high carrier densities indicate rather high
mobilities, many questions pertaining to disorder remain unanswered. In
particular, it has been argued theoretically, that when the average carrier
density is zero, the inescapable presence of disorder will lead to electron and
hole puddles with equal probability. In this work, we use a scanning single
electron transistor to image the carrier density landscape of graphene in the
vicinity of the neutrality point. Our results clearly show the electron-hole
puddles expected theoretically. In addition, our measurement technique enables
to determine locally the density of states in graphene. In contrast to
previously studied massive two dimensional electron systems, the kinetic
contribution to the density of states accounts quantitatively for the measured
signal. Our results suggests that exchange and correlation effects are either
weak or have canceling contributions.Comment: 13 pages, 5 figure
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