Topological Hausdorff dimension and level sets of generic continuous functions on fractals

In an earlier paper we introduced a new concept of dimension for metric spaces, the so called topological Hausdorff dimension. For a compact metric space K let dim H K and dim tH K denote its Hausdorff and topological Hausdorff dimension, respectively. We proved that this new dimension describes the Hausdorff dimension of the level sets of the generic continuous function on K, namely sup{ dimHf- 1(y):y∈R}= dimtHK-1 for the generic f ∈ C(K), provided that K is not totally disconnected, otherwise every non-empty level set is a singleton. We also proved that if K is not totally disconnected and sufficiently homogeneous then dim H f -1(y) = dim tH K - 1 for the generic f ∈ C(K) and the generic y ∈ f(K). The most important goal of this paper is to make these theorems more precise. As for the first result, we prove that the supremum is actually attained on the left hand side of the first equation above, and also show that there may only be a unique level set of maximal Hausdorff dimension. As for the second result, we characterize those compact metric spaces for which for the generic f ∈ C(K) and the generic y ∈ f(K) we have dim H f -1(y) = dim tH K - 1. We also generalize a result of B. Kirchheim by showing that if K is self-similar then for the generic f ∈ C(K) for every y∈intf(K) we have dim H f -1(y) = dim tH K - 1. Finally, we prove that the graph of the generic f ∈ C(K) has the same Hausdorff and topological Hausdorff dimension as K. © 2012 Elsevier Ltd. All rights reserved

TBK1 and IKKε act redundantly to mediate STING-induced NF-κB responses in myeloid cells

Stimulator of Interferon Genes (STING) is a critical component of host innate immune defense but can contribute to chronic autoimmune or autoinflammatory disease. Once activated, the cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) (cGAMP) synthase (cGAS)-STING pathway induces both type I interferon (IFN) expression and nuclear factor-κB (NF-κB)-mediated cytokine production. Currently, these two signaling arms are thought to be mediated by a single upstream kinase, TANK-binding kinase 1 (TBK1). Here, using genetic and pharmacological approaches, we show that TBK1 alone is dispensable for STING-induced NF-κB responses in human and mouse immune cells, as well as in vivo. We further demonstrate that TBK1 acts redundantly with IκB kinase ε (IKKε) to drive NF-κB upon STING activation. Interestingly, we show that activation of IFN regulatory factor 3 (IRF3) is highly dependent on TBK1 kinase activity, whereas NF-κB is significantly less sensitive to TBK1/IKKε kinase inhibition. Our work redefines signaling events downstream of cGAS-STING. Our findings further suggest that cGAS-STING will need to be targeted directly to effectively ameliorate the inflammation underpinning disorders associated with STING hyperactivity

Newton's identities and positivity of trace class integral operators

We provide a countable set of conditions based on elementary symmetric polynomials that are necessary and sufficient for a trace class integral operator to be positive semidefinite, which is an important cornerstone for quantum theory in phase-space representation. We also present a new, efficiently computable algorithm based on Newton's identities. Our test of positivity is much more sensitive than the ones given by the linear entropy and Robertson-Schr\"odinger's uncertainty relations; our first condition is equivalent to the non-negativity of the linear entropy.Comment: 15 pages, 6 figure

Interleukin-1 receptor-associated kinase 4 (IRAK4) plays a dual role in myddosome formation and Toll-like receptor signaling

Toll-like receptors (TLRs) form part of the host innate immune system, in which they act as sensors of microbial and endogenous danger signals. Upon TLR activation, the intracellular Toll/interleukin-1 receptor domains of TLR dimers initiate oligomerization of a multiprotein signaling platform comprising myeloid differentiation primary response 88 (MyD88) and members of the interleukin-1 receptor-associated kinase (IRAK) family. Formation of this myddosome complex initiates signal transduction pathways, leading to the activation of transcription factors and the production of inflammatory cytokines. To date, little is known about the assembly and disassembly of the myddosome and about the mechanisms by which these complexes mediate multiple downstream signaling pathways. Here, we isolated myddosome complexes from whole-cell lysates of TLR-activated primary mouse macrophages and from IRAK reporter macrophages to examine the kinetics of myddosome assembly and disassembly. Using a selective inhibitor of IRAK4\u27s kinase activity, we found that whereas TLR cytokine responses were ablated, myddosome formation was stabilized in the absence of IRAK4\u27s kinase activity. Of note, IRAK4 inhibition had only a minimal effect on NF-kappaB and mitogen-activated protein kinase (MAPK) signaling. In summary, our results indicate that IRAK4 has a critical scaffold function in myddosome formation and that its kinase activity is dispensable for myddosome assembly and activation of the NF-kappaB and MAPK pathways but is essential for MyD88-dependent production of inflammatory cytokines. Our findings suggest that the scaffold function of IRAK4 may be an attractive target for treating inflammatory and autoimmune diseases

Pharmacological inhibition of TBK1/IKKε blunts immunopathology in a murine model of SARS-CoV-2 infection

TANK-binding kinase 1 (TBK1) is a key signalling component in the pro-duction of type-I interferons, which have essential antiviral activities,including against SARS-CoV-2. TBK1, and its homologue IκB kinase-ε (IKKε), can also induce pro-inflammatory responses that contribute to pathogen clearance. While initially protective, sustained engagement of type-I interferons is associated with damaging hyper-inflammation found in severe COVID-19 patients. The contribution of TBK1/IKKε signalling to these responses is unknown. Here we find that the small molecule idronoxil inhibits TBK1/IKKε signalling through destabilisation of TBK1/IKKε protein complexes. Treatment with idronoxil, or the small molecule inhibitor MRT67307, suppresses TBK1/IKKε signalling and attenuates cellular and molecular lung inflammation in SARS-CoV-2-challenged mice. Our findings additionally demonstrate that engagement of STING is not the major driver of these inflammatory responses and establish a critical role for TBK1/IKKε signalling in SARS-CoV-2 hyper inflammation

Determination of the Jet Energy Scale at the Collider Detector at Fermilab

A precise determination of the energy scale of jets at the Collider Detector at Fermilab at the Tevatron $p\bar{p}$ collider is described. Jets are used in many analyses to estimate the energies of partons resulting from the underlying physics process. Several correction factors are developed to estimate the original parton energy from the observed jet energy in the calorimeter. The jet energy response is compared between data and Monte Carlo simulation for various physics processes, and systematic uncertainties on the jet energy scale are determined. For jets with transverse momenta above 50 GeV the jet energy scale is determined with a 3% systematic uncertainty

Conceptual Challenges for Advancing the Socio-Technical Underpinnings of Health Informatics

This discussion paper considers the adoption of socio-technical perspectives and their theoretical and practical influence within the discipline of health informatics. The paper highlights the paucity of discussion of the philosophy, theory and concepts of socio-technical perspectives within health informatics. Instead of a solid theoretical base from which to describe, study and understand human-information technology interactions we continue to have fragmented, unelaborated understandings. This has resulted in a continuing focus on technical system performance and increasingly managerial outputs to the detriment of social and technical systems analysis. It has also limited critical analyses and the adaptation of socio-technical approaches beyond the immediate environment to the broader social systems of contemporary society, an expansion which is increasingly mandated in today’s complex health environment

Social Interactions vs Revisions, What is important for Promotion in Wikipedia?

In epistemic community, people are said to be selected on their knowledge contribution to the project (articles, codes, etc.) However, the socialization process is an important factor for inclusion, sustainability as a contributor, and promotion. Finally, what does matter to be promoted? being a good contributor? being a good animator? knowing the boss? We explore this question looking at the process of election for administrator in the English Wikipedia community. We modeled the candidates according to their revisions and/or social attributes. These attributes are used to construct a predictive model of promotion success, based on the candidates's past behavior, computed thanks to a random forest algorithm. Our model combining knowledge contribution variables and social networking variables successfully explain 78% of the results which is better than the former models. It also helps to refine the criterion for election. If the number of knowledge contributions is the most important element, social interactions come close second to explain the election. But being connected with the future peers (the admins) can make the difference between success and failure, making this epistemic community a very social community too

Measurement of the Helicity Fractions of W Bosons from Top Quark Decays Using Fully Reconstructed top-antitop Events with CDF II

We present a measurement of the fractions F_0 and F_+ of longitudinally polarized and right-handed W bosons in top quark decays using data collected with the CDF II detector. The data set used in the analysis corresponds to an integrated luminosity of approximately 318 pb -1. We select ttbar candidate events with one lepton, at least four jets, and missing transverse energy. Our helicity measurement uses the decay angle theta*, which is defined as the angle between the momentum of the charged lepton in the W boson rest frame and the W momentum in the top quark rest frame. The cos(theta*) distribution in the data is determined by full kinematic reconstruction of the ttbar candidates. We find F_0 = 0.85 +0.15 -0.22 (stat) +- 0.06 (syst) and F_+ = 0.05 +0.11 -0.05 (stat) +- 0.03 (syst), which is consistent with the standard model prediction. We set an upper limit on the fraction of right-handed W bosons of F_+ < 0.26 at the 95% confidence level.Comment: 11 pages, 2 figures, submitted to Phys. Rev.