Learning Arbitrary Statistical Mixtures of Discrete Distributions

We study the problem of learning from unlabeled samples very general statistical mixture models on large finite sets. Specifically, the model to be learned, $\vartheta$, is a probability distribution over probability distributions $p$, where each such $p$ is a probability distribution over $[n] = \{1,2,\dots,n\}$. When we sample from $\vartheta$, we do not observe $p$ directly, but only indirectly and in very noisy fashion, by sampling from $[n]$ repeatedly, independently $K$ times from the distribution $p$. The problem is to infer $\vartheta$ to high accuracy in transportation (earthmover) distance. We give the first efficient algorithms for learning this mixture model without making any restricting assumptions on the structure of the distribution $\vartheta$. We bound the quality of the solution as a function of the size of the samples $K$ and the number of samples used. Our model and results have applications to a variety of unsupervised learning scenarios, including learning topic models and collaborative filtering.Comment: 23 pages. Preliminary version in the Proceeding of the 47th ACM Symposium on the Theory of Computing (STOC15

Extracellular Mechanotransduction

We highlight the force-sensing function of extracellular matrix and present a complementary mechanotransduction paradigm

Disease signatures are robust across tissues and experiments

Meta-analyses combining gene expression microarray experiments offer new insights into the molecular pathophysiology of disease not evident from individual experiments. Although the established technical reproducibility of microarrays serves as a basis for meta-analysis, pathophysiological reproducibility across experiments is not well established. In this study, we carried out a large-scale analysis of disease-associated experiments obtained from NCBI GEO, and evaluated their concordance across a broad range of diseases and tissue types. On evaluating 429 experiments, representing 238 diseases and 122 tissues from 8435 microarrays, we find evidence for a general, pathophysiological concordance between experiments measuring the same disease condition. Furthermore, we find that the molecular signature of disease across tissues is overall more prominent than the signature of tissue expression across diseases. The results offer new insight into the quality of public microarray data using pathophysiological metrics, and support new directions in meta-analysis that include characterization of the commonalities of disease irrespective of tissue, as well as the creation of multi-tissue systems models of disease pathology using public data

Chalcogenide-glass polarization-maintaining photonic crystal fiber for mid-infrared supercontinuum generation

In this paper, we report the design and fabrication of a highly birefringent polarization-maintaining photonic crystal fiber (PM-PCF) made from chalcogenide glass, and its application to linearly-polarized supercontinuum (SC) generation in the mid-infrared region. The PM fiber was drawn using the casting method from As38Se62 glass which features a transmission window from 2 to 10 $\mu m$ and a high nonlinear index of 1.13.10$^{-17}$m$^{2}$W$^{-1}$. It has a zero-dispersion wavelength around 4.5 $\mu m$ and, at this wavelength, a large birefringence of 6.10$^{-4}$ and consequently strong polarization maintaining properties are expected. Using this fiber, we experimentally demonstrate supercontinuum generation spanning from 3.1-6.02 $\mu m$ and 3.33-5.78 $\mu m$ using femtosecond pumping at 4 $\mu m$ and 4.53 $\mu m$, respectively. We further investigate the supercontinuum bandwidth versus the input pump polarization angle and we show very good agreement with numerical simulations of the two-polarization model based on two coupled generalized nonlinear Schr\"odinger equations.Comment: 13 pages, 8 figure

Fueling climate (in)action:How organizations engage in hegemonization to avoid transformational action on climate change

This study examines how organizations avoid the urgent need for transformational action on climate change by engaging in a hegemonization process. To show how this unfolds, we draw from Laclau and Mouffe’s discourse theory, focusing on the case of BP and its engagement with the climate change debate from 1990 to 2015. Our study takes a longitudinal approach to illustrate how BP defended its core business of producing and selling fossil fuel products by enacting three sequential hegemonization strategies. These included: adopting new signifiers; building ‘win-win’ relationships; and adapting nodal points. In doing so, we demonstrate how hegemonic construction enables organizations to both incorporate and evade various types of stakeholder critique, which, we argue, reproduces business-as-usual. Our study contributes to organization studies literature on hegemony by highlighting how the construction of hegemony operates accumulatively over an extended period of time. We also contribute more broadly to conversations around political contests and the natural environment by illustrating how the lack of effective climate responses is shaped by temporal dynamics

Crowdsourcing design guidance for contextual adaptation of text content in augmented reality

Funding Information: This work was supported by EPSRC (grants EP/R004471/1 and EP/S027432/1). Supporting data for this publication is available at https://doi.org/10.17863/CAM.62931.Augmented Reality (AR) can deliver engaging user experiences that seamlessly meld virtual content with the physical environment. However, building such experiences is challenging due to the developer's inability to assess how uncontrolled deployment contexts may infuence the user experience. To address this issue, we demonstrate a method for rapidly conducting AR experiments and real-world data collection in the user's own physical environment using a privacy-conscious mobile web application. The approach leverages the large number of distinct user contexts accessible through crowdsourcing to efciently source diverse context and perceptual preference data. The insights gathered through this method complement emerging design guidance and sample-limited lab-based studies. The utility of the method is illustrated by reexamining the design challenge of adapting AR text content to the user's environment. Finally, we demonstrate how gathered design insight can be operationalized to provide adaptive text content functionality in an AR headset.Publisher PD

Steered Molecular Dynamic Simulations Reveal Marfan Syndrome Mutations Disrupt Fibrillin-1 cbEGF Domain Mechanosensitive Balcium Binding

Marfan syndrome (MFS) is a highly variable genetic connective tissue disorder caused by mutations in the calcium binding extracellular matrix glycoprotein fibrillin-1. Patients with the most severe form of MFS (neonatal MFS; nMFS) tend to have mutations that cluster in an internal region of fibrillin-1 called the neonatal region. This region is predominantly composed of eight calcium-binding epidermal growth factor-like (cbEGF) domains, each of which binds one calcium ion and is stabilized by three highly conserved disulfide bonds. Crucially, calcium plays a fundamental role in stabilizing cbEGF domains. Perturbed calcium binding caused by cbEGF domain mutations is thus thought to be a central driver of MFS pathophysiology. Using steered molecular dynamics (SMD) simulations, we demonstrate that cbEGF domain calcium binding decreases under mechanical stress (i.e. cbEGF domains are mechanosensitive). We further demonstrate the disulfide bonds in cbEGF domains uniquely orchestrate protein unfolding by showing that MFS disulfide bond mutations markedly disrupt normal mechanosensitive calcium binding dynamics. These results point to a potential mechanosensitive mechanism for fibrillin-1 in regulating extracellular transforming growth factor beta (TGFB) bioavailability and microfibril integrity. Such mechanosensitive smart features may represent novel mechanisms for mechanical hemostasis regulation in extracellular matrix that are pathologically activated in MFS

A requirement for bone morphogenetic protein-7 during development of the mammalian kidney and eye.

BMP-7/OP-1, a member of the transforming growth factor-beta (TGF-beta) family of secreted growth factors, is expressed during mouse embryogenesis in a pattern suggesting potential roles in a variety of inductive tissue interactions. The present study demonstrates that mice lacking BMP-7 display severe defects confined to the developing kidney and eye. Surprisingly, the early inductive tissue interactions responsible for establishing both organs appear largely unaffected. However, the absence of BMP-7 disrupts the subsequent cellular interactions required for their continued growth and development. Consequently, homozygous mutant animals exhibit renal dysplasia and anophthalmia at birth. Overall, these findings identify BMP-7 as an essential signaling molecule during mammalian kidney and eye development

On the Hausdorff dimension of invariant measures of weakly contracting on average measurable IFS

We consider measures which are invariant under a measurable iterated function system with positive, place-dependent probabilities in a separable metric space. We provide an upper bound of the Hausdorff dimension of such a measure if it is ergodic. We also prove that it is ergodic iff the related skew product is.Comment: 16 pages; to appear in Journal of Stat. Phy