TMC-1C: an accreting starless core

We have mapped the starless core TMC-1C in a variety of molecular lines with the IRAM 30m telescope. High density tracers show clear signs of self-absorption and sub-sonic infall asymmetries are present in N2H+ (1-0) and DCO+ (2-1) lines. The inward velocity profile in N2H+ (1-0) is extended over a region of about 7,000 AU in radius around the dust continuum peak, which is the most extended ``infalling'' region observed in a starless core with this tracer. The kinetic temperature (~12 K) measured from C17O and C18O suggests that their emission comes from a shell outside the colder interior traced by the mm continuum dust. The C18O (2-1) excitation temperature drops from 12 K to ~10 K away from the center. This is consistent with a volume density drop of the gas traced by the C18O lines, from ~4x10^4 cm^-3 towards the dust peak to ~6x10^3 cm^-3 at a projected distance from the dust peak of 80" (or 11,000 AU). The column density implied by the gas and dust show similar N2H+ and CO depletion factors (f_D < 6). This can be explained with a simple scenario in which: (i) the TMC-1C core is embedded in a relatively dense environment (H2 ~10^4 cm^-3), where CO is mostly in the gas phase and the N2H+ abundance had time to reach equilibrium values; (ii) the surrounding material (rich in CO and N2H+) is accreting onto the dense core nucleus; (iii) TMC-1C is older than 3x10^5 yr, to account for the observed abundance of N2H+ across the core (~10^-10 w.r.t. H2); and (iv) the core nucleus is either much younger (~10^4 yr) or ``undepleted'' material from the surrounding envelope has fallen towards it in the past 10,000 yr.Comment: 29 pages, including 5 tables and 15 figure

Epithelial cell dysfunction, a major driver of asthma development

Airway epithelial barrier dysfunction is frequently observed in asthma and may have important implications. The physical barrier function of the airway epithelium is tightly interwoven with its immunomodulatory actions, while abnormal epithelial repair responses may contribute to remodelling of the airway wall. We propose that abnormalities in the airway epithelial barrier play a crucial role in the sensitization to allergens and pathogenesis of asthma. Many of the identified susceptibility genes for asthma are expressed in the airway epithelium, supporting the notion that events at the airway epithelial surface are critical for the development of the disease. However, the exact mechanisms by which the expression of epithelial susceptibility genes translates into a functionally altered response to environmental risk factors of asthma are still unknown. Interactions between genetic factors and epigenetic regulatory mechanisms may be crucial for asthma susceptibility. Understanding these mechanisms may lead to identification of novel targets for asthma intervention by targeting the airway epithelium. Moreover, exciting new insights have come from recent studies using single-cell RNA sequencing (scRNA-Seq) to study the airway epithelium in asthma. This review focuses on the role of airway epithelial barrier function in the susceptibility to develop asthma and novel insights in the modulation of epithelial cell dysfunction in asthma

Thoria-based cermet nuclear fuel : sintered microsphere fabrication by spray drying.

Cermet nuclear fuels have been demonstrated to have significant potential to enhance fuel performance because of low internal fuel temperatures and low stored energy. The combination of these benefits with the inherent proliferation resistance, high burnup capability, and favorable neutronic properties of the thorium fuel cycle produces intriguing options for advanced nuclear fuel cycles. This paper describes aspects of a Nuclear Energy Research Initiative (NERI) project with two primary goals: (1) Evaluate the feasibility of implementing the thorium fuel cycle in existing or advanced reactors using a zirconium-matrix cermet fuel, and (2) Develop enabling technologies required for the economic application of this new fuel form. Spray drying is a physical process of granulating fine powders that is used widely in the chemical, pharmaceutical, ceramic, and food industries. It is generally used to produce flowable fine powders. Occasionally it is used to fabricate sintered bodies like cemented carbides, but it has not, heretofore, been used to produce sintered microspheres. As a physical process, it can be adapted to many powder types and mixtures and thus, has appeal for nuclear fuels and waste forms of various compositions. It also permits easy recycling of process ''wastes'' and minimal chemical waste streams that can arise in chemical sol/gel processing. On the other hand, for radioactive powders, it presents safety challenges for processing these materials in powder form and in achieving microspheres of high density and perfection

Unseen Classes at a Later Time? No Problem

Recent progress towards learning from limited supervision has encouraged efforts towards designing models that can recognize novel classes at test time (generalized zero-shot learning or GZSL). GZSL approaches assume knowledge of all classes, with or without labeled data, beforehand. However, practical scenarios demand models that are adaptable and can handle dynamic addition of new seen and unseen classes on the fly (i.e continual generalized zero-shot learning or CGZSL). One solution is to sequentially retrain and reuse conventional GZSL methods, however, such an approach suffers from catastrophic forgetting leading to suboptimal generalization performance. A few recent efforts towards tackling CGZSL have been limited by difference in settings, practicality, data splits and protocols followed - inhibiting fair comparison and a clear direction forward. Motivated from these observations, in this work, we firstly consolidate the different CGZSL setting variants and propose a new Online-CGZSL setting which is more practical and flexible. Secondly, we introduce a unified feature-generative framework for CGZSL that leverages bi-directional incremental alignment to dynamically adapt to addition of new classes, with or without labeled data, that arrive over time in any of these CGZSL settings. Our comprehensive experiments and analysis on five benchmark datasets and comparison with baselines show that our approach consistently outperforms existing methods, especially on the more practical Online setting. © 2022 IEEE

Inhibition of beta-Catenin/CREB Binding Protein Signaling Attenuates House Dust Mite-Induced Goblet Cell Metaplasia in Mice

Excessive mucus production is a major feature of allergic asthma. Disruption of epithelial junctions by allergens such as house dust mite (HDM) results in the activation of β-catenin signaling, which has been reported to stimulate goblet cell differentiation. β-catenin interacts with various co-activators including CREB binding protein (CBP) and p300, thereby regulating the expression of genes involved in cell proliferation and differentiation, respectively. We specifically investigated the role of the β-catenin/CBP signaling pathway in goblet cell metaplasia in a HDM-induced allergic airway disease model in mice using ICG-001, a small molecule inhibitor that blocks the binding of CBP to β-catenin. Female 6- 8-week-old BALB/c mice were sensitized to HDM/saline on days 0, 1, and 2, followed by intranasal challenge with HDM/saline with or without subcutaneous ICG-001/vehicle treatment from days 14 to 17, and samples harvested 24 h after the last challenge/treatment. Differential inflammatory cells in bronchoalveolar lavage (BAL) fluid were enumerated. Alcian blue (AB)/Periodic acid–Schiff (PAS) staining was used to identify goblet cells/mucus production, and airway hyperresponsiveness (AHR) was assessed using invasive plethysmography. Exposure to HDM induced airway inflammation, goblet cell metaplasia and increased AHR, with increased airway resistance in response to the non-specific spasmogen methacholine. Inhibition of the β-catenin/CBP pathway using treatment with ICG-001 significantly attenuated the HDM-induced goblet cell metaplasia and infiltration of macrophages, but had no effect on eosinophils, neutrophils, lymphocytes or AHR. Increased β-catenin/CBP signaling may promote HDM-induced goblet cell metaplasia in mice

Mapping the spatiotemporal dynamics of calcium signaling in cellular neural networks using optical flow

An optical flow gradient algorithm was applied to spontaneously forming net- works of neurons and glia in culture imaged by fluorescence optical microscopy in order to map functional calcium signaling with single pixel resolution. Optical flow estimates the direction and speed of motion of objects in an image between subsequent frames in a recorded digital sequence of images (i.e. a movie). Computed vector field outputs by the algorithm were able to track the spatiotemporal dynamics of calcium signaling pat- terns. We begin by briefly reviewing the mathematics of the optical flow algorithm, and then describe how to solve for the displacement vectors and how to measure their reliability. We then compare computed flow vectors with manually estimated vectors for the progression of a calcium signal recorded from representative astrocyte cultures. Finally, we applied the algorithm to preparations of primary astrocytes and hippocampal neurons and to the rMC-1 Muller glial cell line in order to illustrate the capability of the algorithm for capturing different types of spatiotemporal calcium activity. We discuss the imaging requirements, parameter selection and threshold selection for reliable measurements, and offer perspectives on uses of the vector data.Comment: 23 pages, 5 figures. Peer reviewed accepted version in press in Annals of Biomedical Engineerin