Cutaneous sarcoidosis simulating porokeratosis of Mibelli

We report a skin localization of systemic sarcoidosis, which presented with lesions that resemble porokeratosis of Mibelli. Skin biopsy showed noncaseating sarcoidal granuloma. Whereas cutaneous sarcoidosis is present in up to one-third of cases and may present with a wide variety of lesions, our presentation is uncommon. Partial remission was obtained with  hydroxychloroquine and prednison

Fire performance of blind-bolted connections to concrete filled tubular columns in tension

This paper describes an advanced numerical model to predict the fire behaviour of blind-bolts in the tension area of endplate connections between I-beams and concrete filled tubular (CFT) columns. It is the continuation of a previous research on the thermal response of connections, considering the tension load of a moment-resisting connection. Due to the absence of experiments and data on blind-bolts fire performance the aim was to provide a model for their study. The effect of two main variables was researched, the concrete infill of the columns and the anchored extension of the blind-bolt. The fire resis- tance rating (FRR), the failure mode and the force–displacement–temperature curve at high temperatures were discussed. Results proved that concrete inside the column enhanced the connections response at elevated temperatures in terms of FRR and stiffness. On the other hand, the use of anchored blind-bolts compared with normal blind-bolts provided stiffer connections, but the FRR improvement depended on the plate thickness and steel bolt properties. Finally, the use of fire resistant steel bolts as a method to enhance the fire response was assessed, observing the benefits to these connections when the shank of the blind-bolt governs the failure

Visual Reasoning with Multi-hop Feature Modulation

Recent breakthroughs in computer vision and natural language processing have spurred interest in challenging multi-modal tasks such as visual question-answering and visual dialogue. For such tasks, one successful approach is to condition image-based convolutional network computation on language via Feature-wise Linear Modulation (FiLM) layers, i.e., per-channel scaling and shifting. We propose to generate the parameters of FiLM layers going up the hierarchy of a convolutional network in a multi-hop fashion rather than all at once, as in prior work. By alternating between attending to the language input and generating FiLM layer parameters, this approach is better able to scale to settings with longer input sequences such as dialogue. We demonstrate that multi-hop FiLM generation achieves state-of-the-art for the short input sequence task ReferIt --- on-par with single-hop FiLM generation --- while also significantly outperforming prior state-of-the-art and single-hop FiLM generation on the GuessWhat?! visual dialogue task.Comment: In Proc of ECCV 201

Thermal behaviour of blind-bolted connections to hollow and concrete-filled steel tubular columns

This paper reports on the thermal analysis of blind-bolts connected to concrete filled steel tube (CFST) and hollow steel section (HSS) columns. The aim is therefore the investigation of the temperature distribution in the connected sections and the evaluation of the effects due to concrete filling and anchored bolt extension. For this purpose, experimental and numerical work was carried out. The test programme involved twelve small- scale unloaded specimens where the variables were: tube section dimensions, type of blind-bolt, and hollow or concrete filled steel tubes. Results from the experiments revealed the noteworthy effect of concrete on bolt temperature reduction, the insignificant influence of tube section dimensions, and the limited impact of embedded bolt extension. Finite element models (FEM) of connections were developed to simulate the behaviour of tested pieces. Comparison with tests allowed the calibration of thermal material properties and characteristics of heat flux in interactions. Furthermore, assessments of heat transfer problem on the simulation of small-scale pieces extended to the numerical model of the whole endplate connection between an I-beam and a tubular column. Finally, the suitability of simple methods from Eurocode 3 Part 1.2 and other references to obtain the temperature on the connection was evaluated

Innate and adaptive humoral responses coat distinct commensal bacteria with immunoglobulin A

Immunoglobulin A (IgA) is prominently secreted at mucosal surfaces and coats a fraction of the intestinal microbiota. However, the commensal bacteria bound by IgA are poorly characterized and the type of humoral immunity they elicit remains elusive. We used bacterial flow cytometry coupled with 16S rRNA gene sequencing (IgA-Seq) in murine models of immunodeficiency to identify IgA-bound bacteria and elucidate mechanisms of commensal IgA targeting. We found that residence in the small intestine, rather than bacterial identity, dictated induction of specific IgA. Most commensals elicited strong T-independent (TI) responses that originated from the orphan B1b lineage and from B2 cells, but excluded natural antibacterial B1a specificities. Atypical commensals including segmented filamentous bacteria and Mucispirillum evaded TI responses but elicited T-dependent IgA. These data demonstrate exquisite targeting of distinct commensal bacteria by multiple layers of humoral immunity and reveal a specialized function of the B1b lineage in TI mucosal IgA responses

Managing data for the international, multicentre INTERGROWTH-21st Project

The INTERGROWTH-21st Project data management was structured incorporating both a centralised and decentralised system for the eight study centres, which all used the same database and standardised data collection instruments, manuals and processes. Each centre was responsible for the entry and validation of their country-specific data, which were entered onto a centralised system maintained by the Data Coordinating Unit in Oxford. A comprehensive data management system was designed to handle the very large volumes of data. It contained internal validations to prevent incorrect and inconsistent values being captured, and allowed online data entry by local Data Management Units, as well as real-time management of recruitment and data collection by the Data Coordinating Unit in Oxford. To maintain data integrity, only the Data Coordinating Unit in Oxford had access to all the eight centres’ data, which were continually monitored. All queries identified were raised with the relevant local data manager for verification and correction, if necessary. The system automatically logged an audit trail of all updates to the database with the date and name of the person who made the changes. These rigorous processes ensured that the data collected in the INTERGROWTH-21st Project were of exceptionally high quality

On non-local variational problems with lack of compactness related to non-linear optics

We give a simple proof of existence of solutions of the dispersion manage- ment and diffraction management equations for zero average dispersion, respectively diffraction. These solutions are found as maximizers of non-linear and non-local vari- ational problems which are invariant under a large non-compact group. Our proof of existence of maximizer is rather direct and avoids the use of Lions' concentration compactness argument or Ekeland's variational principle.Comment: 30 page

Reprogramming of CTLs into natural killer–like cells in celiac disease

Celiac disease is an intestinal inflammatory disorder induced by dietary gluten in genetically susceptible individuals. The mechanisms underlying the massive expansion of interferon γ–producing intraepithelial cytotoxic T lymphocytes (CTLs) and the destruction of the epithelial cells lining the small intestine of celiac patients have remained elusive. We report massive oligoclonal expansions of intraepithelial CTLs that exhibit a profound genetic reprogramming of natural killer (NK) functions. These CTLs aberrantly expressed cytolytic NK lineage receptors, such as NKG2C, NKp44, and NKp46, which associate with adaptor molecules bearing immunoreceptor tyrosine-based activation motifs and induce ZAP-70 phosphorylation, cytokine secretion, and proliferation independently of T cell receptor signaling. This NK transformation of CTLs may underlie both the self-perpetuating, gluten-independent tissue damage and the uncontrolled CTL expansion leading to malignant lymphomas in severe forms of celiac disease. Because similar changes were detected in a subset of CTLs from cytomegalovirus-seropositive patients, we suggest that a stepwise transformation of CTLs into NK-like cells may underlie immunopathology in various chronic infectious and inflammatory diseases

GATA4 controls regionalization of tissue immunity and commensal-driven immunopathology

There is growing recognition that regionalization of bacterial colonization and immunity along the intestinal tract has an important role in health and disease. Yet, the mechanisms underlying intestinal regionalization and its dysregulation in disease are not well understood. This study found that regional epithelial expression of the transcription factor GATA4 controls bacterial colonization and inflammatory tissue immunity in the proximal small intestine by regulating retinol metabolism and luminal IgA. Furthermore, in mice without jejunal GATA4 expression, the commensal segmented filamentous bacteria promoted pathogenic inflammatory immune responses that disrupted barrier function and increased mortality upon Citrobacter rodentium infection. In celiac disease patients, low GATA4 expression was associated with metabolic alterations, mucosal Actinobacillus, and increased IL-17 immunity. Taken together, these results reveal broad impacts of GATA4-regulated intestinal regionalization on bacterial colonization and tissue immunity, highlighting an elaborate interdependence of intestinal metabolism, immunity, and microbiota in homeostasis and disease.</p