Aberrant innate immune sensing leads to the rapid progression of idiopathic pulmonary fibrosis

Novel approaches are needed to define subgroups of patients with Idiopathic pulmonary fibrosis (IPF) at risk for acute exacerbations and/or accelerated progression of this generally fatal disease. Progression of disease is an integral component of IPF with a median survival of 3 to 5 years. Conversely, a high degree of variability in disease progression has been reported among series. The characteristics of patients at risk of earlier death predominantly rely on baseline HRCT appearance, but this concept that has been challenged. Disparate physiological approaches have also been taken to identify patients at risk of mortality, with varying results. We hypothesized that the rapid decline in lung function in IPF may be a consequence of an abnormal host response to pathogen-associated molecular patterns (PAMPs), leading to aberrant activation in fibroblasts and fibrosis. Analysis of upper and lower lobe surgical lung biopsies (SLBs) indicated that TLR9, a hypomethylated CpG DNA receptor, is prominently expressed at the transcript and protein level, most notably in biopsies from rapidly progressive IPF patients. Surprisingly, fibroblasts appeared to be a major cellular source of TLR9 expression in IPF biopsies from this group of progressors. Further, CpG DNA promoted profibrotic cytokine and chemokine synthesis in isolated human IPF fibroblasts, most markedly again in cells from patients with the rapidly progressive IPF phenotype, in a TLR9-dependent manner. Finally, CpG DNA exacerbated fibrosis in an in vivo model initiated by the adoptive transfer of primary fibroblasts derived from patients who exhibited rapidly progressing fibrosis. Together, these data suggested that TLR9 activation via hypomethylated DNA might be an important mechanism in promoting fibrosis particularly in patients prone to rapidly progressing IPF

Proper motions of the HH1 jet

We describe a new method for determining proper motions of extended objects, and a pipeline developed for the application of this method. We then apply this method to an analysis of four epochs of [S~II] HST images of the HH~1 jet (covering a period of $\sim 20$~yr). We determine the proper motions of the knots along the jet, and make a reconstruction of the past ejection velocity time-variability (assuming ballistic knot motions). This reconstruction shows an "acceleration" of the ejection velocities of the jet knots, with higher velocities at more recent times. This acceleration will result in an eventual merging of the knots in $\sim 450$~yr and at a distance of $\sim 80"$ from the outflow source, close to the present-day position of HH~1.Comment: 12 pages, 8 figure

Science Requirement Document for the European Solar Telescope

The European Solar Telescope (EST)1 is a research infrastructure for solar physics. It is planned to be an on-axis solar telescope with an aperture of 4m and equipped with an innovative suite of spectro-polarimetric and imaging post-focus instrumentation. The EST project was initiated and is driven by EAST2, the European Association for Solar Telescopes. EAST was founded in 2006 as an association of 14 European countries. Today, as of December 2019, EAST consists of 26 European research institutes from 18 European countries. The Preliminary Design Phase of EST was accomplished between 2008 and 2011. During this phase, in 2010, the first version of the EST Science Requirement Document (SRD)was published. After EST became a project on the ESFRI3 roadmap 2016, the preparatory phase started. This phase is partially supported by EU funding through the PRE-EST H2020 project4. The goal of the preparatory phase is to accomplish a final design for the telescope and the legal governance structure of EST. A major milestone on this path is to revisit and update the Science Requirement Document (SRD). The EST Science Advisory Group (SAG) has been constituted by EAST and the Board of the PRE-EST4 EU project in November 2017 and has been charged with the task of providing with a final statement on the science requirements for EST. Based on the conceptual design, the SRD update takes into account recent technical and scientific developments, to ensure that EST provides significant advancement beyond the current state-of-the-art. The present update of the EST SRD has been developed and discussed during a series of EST SAG meetings: 1st telecon meeting on Nov 5th, 2017 2nd meeting in Freiburg, Nov 24, 2017 3rd telecon meeting, Dec 15, 2017 4th telecon meeting, March 26, 2018 5th meeting in Belfast, April 16 & 17, 2018 6th meeting in Naxos, June 16, 2018 7th telecon meeting, January 14, 2019 8th telecon meeting, October 11, 2019 9th telecon meeting, October 22, 2019 10th telecon meeting, December 3, 2019 The SRD develops the top-level science objectives of EST into individual science cases. Identifying critical science requirements is one of its main goals. Those requirements will define the capabilities of EST and the post-focus instrument suite. The technical requirements for the final design of EST will be derived from the SRD. The science cases presented in Part II (Sects. 1 to 8) are not intended to cover all the science questions to be addressed with EST, but rather to provide a precise overview of the capabilities that will make of EST a competitive state-of-the-art telescope to push the boundaries of our knowledge over the next few decades. The science cases contain detailed observing programmes specifying the type of observations needed to solve specific science problems. An eort is being made to define the parameters of the required observations as accurately as possible, taking into account both present capabilities and technological developments expected in the near future. The tables of the observing programmes corresponding to the science cases are compiled in Sect. 10. The EST science cases represent challenging observations that put strong constraints on the telescope and its instrument suite. Ultimately, they will be translated into Technical Requirement Document (TRD) leading to the final EST design to be implemented during the construction phase. The unique design advantages of the EST concept is presented in Section 11. The eect of the science cases on the EST design are discussed in Section 12 and summarized in Section 13.This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 739 50

Evolution of Galactic Discs: Multiple Patterns, Radial Migration and Disc Outskirts

We investigate the evolution of galactic disks in N-body Tree-SPH simulations. We find that disks, initially truncated at three scale-lengths, can triple their radial extent, solely driven by secular evolution. Both Type I (single exponential) and Type II (down-turning) observed disk surface-brightness profiles can be explained by our findings. We relate these results to the strong angular momentum outward transfer, resulting from torques and radial migration associated with multiple patterns, such as central bars and spiral waves of different multiplicity. We show that even for stars ending up on cold orbits, the changes in angular momentum exhibit complex structure as a function of radius, unlike the expected effect of transient spirals alone. Focussing on one of our models, we find evidence for non-linear coupling among m=1, 2, 3 and 4 density waves, where m is the pattern multiplicity. We suggest that the naturally occurring larger resonance widths at galactic radii beyond four scale-lengths may have profound consequences on the formation and location of breaks in disk density profiles, provided spirals are present at such large distances. We also consider the effect of gas inflow and show that when in-plane smooth gas accretion of ~5 M_sun/yr is included, the outer disks become more unstable, leading to a strong increase in the stellar velocity dispersion. This, in turn, causes the formation of a Type III (up-turning) profile in the old stellar population. We propose that observations of Type III surface brightness profiles, combined with an up-turn in the stellar velocity dispersions beyond the disk break, could be a signature of ongoing gas-accretion. The results of this study suggest that disk outskirts comprised of stars migrated from the inner disk would have relatively large radial velocity dispersions, and significant thickness when seen edge-on. [Abridged]Comment: Replaced with accepted version. New Fig. 5 added, Section 10 decreased in size, old Fig. 17 removed. Conclusions remain the same. High-resolution version can be found at http://www.ivanminchev.co

Small-scale solar magnetic fields

As we resolve ever smaller structures in the solar atmosphere, it has become clear that magnetism is an important component of those small structures. Small-scale magnetism holds the key to many poorly understood facets of solar magnetism on all scales, such as the existence of a local dynamo, chromospheric heating, and flux emergence, to name a few. Here, we review our knowledge of small-scale photospheric fields, with particular emphasis on quiet-sun field, and discuss the implications of several results obtained recently using new instruments, as well as future prospects in this field of research.Comment: 43 pages, 18 figure

Multiwavelength studies of MHD waves in the solar chromosphere: An overview of recent results

The chromosphere is a thin layer of the solar atmosphere that bridges the relatively cool photosphere and the intensely heated transition region and corona. Compressible and incompressible waves propagating through the chromosphere can supply significant amounts of energy to the interface region and corona. In recent years an abundance of high-resolution observations from state-of-the-art facilities have provided new and exciting ways of disentangling the characteristics of oscillatory phenomena propagating through the dynamic chromosphere. Coupled with rapid advancements in magnetohydrodynamic wave theory, we are now in an ideal position to thoroughly investigate the role waves play in supplying energy to sustain chromospheric and coronal heating. Here, we review the recent progress made in characterising, categorising and interpreting oscillations manifesting in the solar chromosphere, with an impetus placed on their intrinsic energetics.Comment: 48 pages, 25 figures, accepted into Space Science Review

Visual Exploration and Object Recognition by Lattice Deformation

Mechanisms of explicit object recognition are often difficult to investigate and require stimuli with controlled features whose expression can be manipulated in a precise quantitative fashion. Here, we developed a novel method (called “Dots”), for generating visual stimuli, which is based on the progressive deformation of a regular lattice of dots, driven by local contour information from images of objects. By applying progressively larger deformation to the lattice, the latter conveys progressively more information about the target object. Stimuli generated with the presented method enable a precise control of object-related information content while preserving low-level image statistics, globally, and affecting them only little, locally. We show that such stimuli are useful for investigating object recognition under a naturalistic setting – free visual exploration – enabling a clear dissociation between object detection and explicit recognition. Using the introduced stimuli, we show that top-down modulation induced by previous exposure to target objects can greatly influence perceptual decisions, lowering perceptual thresholds not only for object recognition but also for object detection (visual hysteresis). Visual hysteresis is target-specific, its expression and magnitude depending on the identity of individual objects. Relying on the particular features of dot stimuli and on eye-tracking measurements, we further demonstrate that top-down processes guide visual exploration, controlling how visual information is integrated by successive fixations. Prior knowledge about objects can guide saccades/fixations to sample locations that are supposed to be highly informative, even when the actual information is missing from those locations in the stimulus. The duration of individual fixations is modulated by the novelty and difficulty of the stimulus, likely reflecting cognitive demand