Chandra Early-Type Galaxy Atlas

The hot ISM in early type galaxies (ETGs) plays a crucial role in understanding their formation and evolution. The structural features of the hot gas identified by Chandra observations point to key evolutionary mechanisms, (e.g., AGN and stellar feedback, merging history). In our Chandra Galaxy Atlas (CGA) project, taking full advantage of the Chandra capabilities, we systematically analyzed the archival Chandra data of 70 ETGs and produced uniform data products for the hot gas properties. The primary data products are spatially resolved 2D spectral maps of the hot gas from individual galaxies. We emphasize that new features can be identified in the spectral maps which are not readily visible in the surface brightness maps. The high-level images can be viewed at the dedicated CGA website, and the CGA data products can be downloaded to compare with data at other wavelengths and to perform further analyses. Utilizing our data products, we address a few focused science topics.Comment: 52 pages, 9 figures, accepted in ApJ Supp

QUERYARCH3D: QUERYING AND VISUALISING 3D MODELS OF A MAYA ARCHAEOLOGICAL SITE IN A WEB-BASED INTERFACE

Constant improvements in the field of surveying, computing and distribution of digital-content are reshaping the way Cultural Heritage can be digitised and virtually accessed, even remotely via web. A traditional 2D approach for data access, exploration, retrieval and exploration may generally suffice, however more complex analyses concerning spatial and temporal features require 3D tools, which, in some cases, have not yet been implemented or are not yet generally commercially available. Efficient organisation and integration strategies applicable to the wide array of heterogeneous data in the field of Cultural Heritage represent a hot research topic nowadays. This article presents a visualisation and query tool (QueryArch3D) conceived to deal with multi-resolution 3D models. Geometric data are organised in successive levels of detail (LoD), provided with geometric and semantic hierarchies and enriched with attributes coming from external data sources. The visualisation and query front-end enables the 3D navigation of the models in a virtual environment, as well as the interaction with the objects by means of queries based on attributes or on geometries. The tool can be used as a standalone application, or served through the web. The characteristics of the research work, along with some implementation issues and the developed QueryArch3D tool will be discussed and presented

A WEB-BASED INTERACTIVE TOOL FOR MULTI-RESOLUTION 3D MODELS OF A MAYA ARCHAEOLOGICAL SITE

Continuous technological advances in surveying, computing and digital-content delivery are strongly contributing to a change in the way Cultural Heritage is “perceived”: new tools and methodologies for documentation, reconstruction and research are being created to assist not only scholars, but also to reach more potential users (e.g. students and tourists) willing to access more detailed information about art history and archaeology. 3D computer-simulated models, sometimes set in virtual landscapes, offer for example the chance to explore possible hypothetical reconstructions, while on-line GIS resources can help interactive analyses of relationships and change over space and time. While for some research purposes a traditional 2D approach may suffice, this is not the case for more complex analyses concerning spatial and temporal features of architecture, like for example the relationship of architecture and landscape, visibility studies etc. The project aims therefore at creating a tool, called “QueryArch3D” tool, which enables the web-based visualisation and queries of an interactive, multi-resolution 3D model in the framework of Cultural Heritage. More specifically, a complete Maya archaeological site, located in Copan (Honduras), has been chosen as case study to test and demonstrate the platform’s capabilities. Much of the site has been surveyed and modelled at different levels of detail (LoD) and the geometric model has been semantically segmented and integrated with attribute data gathered from several external data sources. The paper describes the characteristics of the research work, along with its implementation issues and the initial results of the developed prototype

Automated conduction velocity estimation based on isochronal activation of heart chambers

Background Spatial differences in conduction velocity (CV) are critical for cardiac arrhythmias induction. We propose a method for an automated CV calculation to identify areas of slower conduction during cardiac arrhythmias and sinus rhythm.Methods Color-coded representations of the isochronal activation map using data coming from the RHYTHMIA (TM) Mapping System were reproduced by applying a temporal isochronal window at 20 ms. Geodesic distances of the 3D mesh were calculated using an algorithm selecting the minimum distance pathway (MDP). The CV estimation was performed considering points on the boundary of two spatially and temporally adjacent isochrones. For each of the boundary points of a given isochrone, the nearest boundary point of the consecutive isochrone was chosen, the MDP was evaluated, and a map of CV was created. The proposed method has been applied to a population of 29 patients.Results In all cases of perimitral atrial flutter (16 pts out of 29 (55%)), areas with significantly low CV (< 30 cm/s) were found. Half of the cases present regions with low CV located in the anterior wall. No case with low CV at the so-called LA isthmus was observed. Right atrial maps during common atrial flutters showed low CV areas mainly located in the inferior inter-atrial septum. No areas of low CV were observed in subjects without a history of atrial arrhythmia while pts affected by paroxysmal AF showed areas with a limited extension of low CV.Conclusions The proposed software for automated CV estimation allows the identification of low CV areas, potentially helping electrophysiologists to plan the ablation strategy

Culture modulates face scanning during dyadic social interactions

Recent studies have revealed significant cultural modulations on face scanning strategies, thereby challenging the notion of universality in face perception. Current findings are based on screen-based paradigms, which offer high degrees of experimental control, but lack critical characteristics common to social interactions (e.g., social presence, dynamic visual saliency), and complementary approaches are required. The current study used head-mounted eye tracking techniques to investigate the visual strategies for face scanning in British/Irish (in the UK) and Japanese adults (in Japan) who were engaged in dyadic social interactions with a local research assistant. We developed novel computational data pre-processing tools and data-driven analysis techniques based on Monte Carlo permutation testing. The results revealed significant cultural differences in face scanning during social interactions for the first time, with British/Irish participants showing increased mouth scanning and the Japanese group engaging in greater eye and central face looking. Both cultural groups further showed more face orienting during periods of listening relative to speaking, and during the introduction task compared to a storytelling game, thereby replicating previous studies testing Western populations. Altogether, these findings point to the significant role of postnatal social experience in specialised face perception and highlight the adaptive nature of the face processing system

A Novel Method of Isolating Myofibrils From Primary Cardiomyocyte Culture Suitable for Myofibril Mechanical Study

Myofibril based mechanical studies allow evaluation of sarcomeric protein function. We describe a novel method of obtaining myofibrils from primary cardiomyocyte culture. Adult rat ventricular myocytes (ARVMs) were obtained by enzymatic digestion and maintained in serum free condition. ARVMs were homogenized in relaxing solution (pCa 9.0) with 20% sucrose, and myofibril suspension was made. Myofibrils were Ca2+-activated and relaxed at 15°C. Results from ARVM myofibrils were compared to myofibrils obtained from ventricular tissue skinned with Triton X-100. At maximal Ca2+-activation (pCa 4.5) myofibril mechanical parameters from ARVMs were 6.8 ± 0.9 mN/mm2 (resting tension), 146.8 ± 13.8 mN/mm2 (maximal active tension, P0), 5.4 ± 0.22 s−1 (rate of force activation), 53.4 ± 4.4 ms (linear relaxation duration), 0.69 ± 0.36 s−1 (linear relaxation rate), and 10.8 ± 1.3 s−1 (exponential relaxation rate). Force-pCa curves were constructed from Triton skinned tissue, ARVM culture day 1, and ARVM culture day 3 myofibrils, and pCa50 were 5.79 ± 0.01, 5.69 ± 0.01, and 5.71 ± 0.01, respectively. Mechanical parameters from myofibrils isolated from ARVMs treated with phenylephrine were compared to myofibrils isolated from time-matched non-treated ARVMs. Phenylephrine treatment did not change the kinetics of activation or relaxation but decreased the pCa50 to 5.56 ± 0.03 (vehicle treated control: 5.67 ± 0.03). For determination of protein expression and post-translational modifications, myofibril slurry was re-suspended and resolved for immunoblotting and protein staining. Troponin I phosphorylation was significantly increased at serine 23/24 in phenylephrine treated group. Myofibrils obtained from ARVMs are a viable method to study myofibril mechanics. Phenylephrine treatment led to significant decrease in Ca2+-sensitivity that is due to increased phosphorylation of TnI at serine 23/24. This culture based approach to obtaining myofibrils will allow pharmacological and genetic manipulation of the cardiomyocytes to correlate biochemical and biophysical properties

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

CXCR4 involvement in neurodegenerative diseases

Neurodegenerative diseases likely share common underlying pathobiology. Although prior work has identified susceptibility loci associated with various dementias, few, if any, studies have systematically evaluated shared genetic risk across several neurodegenerative diseases. Using genome-wide association data from large studies (total n = 82,337 cases and controls), we utilized a previously validated approach to identify genetic overlap and reveal common pathways between progressive supranuclear palsy (PSP), frontotemporal dementia (FTD), Parkinson's disease (PD) and Alzheimer's disease (AD). In addition to the MAPT H1 haplotype, we identified a variant near the chemokine receptor CXCR4 that was jointly associated with increased risk for PSP and PD. Using bioinformatics tools, we found strong physical interactions between CXCR4 and four microglia related genes, namely CXCL12, TLR2, RALB, and CCR5. Evaluating gene expression from post-mortem brain tissue, we found that expression of CXCR4 and microglial genes functionally related to CXCR4 was dysregulated across a number of neurodegenerative diseases. Furthermore, in a mouse model of tauopathy, expression of CXCR4 and functionally associated genes was significantly altered in regions of the mouse brain that accumulate neurofibrillary tangles most robustly. Beyond MAPT, we show dysregulation of CXCR4 expression in PSP, PD, and FTD brains, and mouse models of tau pathology. Our multi-modal findings suggest that abnormal signaling across a 'network' of microglial genes may contribute to neurodegeneration and may have potential implications for clinical trials targeting immune dysfunction in patients with neurodegenerative diseases

Immune-related genetic enrichment in frontotemporal dementia: An analysis of genome-wide association studies.

BACKGROUND: Converging evidence suggests that immune-mediated dysfunction plays an important role in the pathogenesis of frontotemporal dementia (FTD). Although genetic studies have shown that immune-associated loci are associated with increased FTD risk, a systematic investigation of genetic overlap between immune-mediated diseases and the spectrum of FTD-related disorders has not been performed. METHODS AND FINDINGS: Using large genome-wide association studies (GWASs) (total n = 192,886 cases and controls) and recently developed tools to quantify genetic overlap/pleiotropy, we systematically identified single nucleotide polymorphisms (SNPs) jointly associated with FTD-related disorders-namely, FTD, corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), and amyotrophic lateral sclerosis (ALS)-and 1 or more immune-mediated diseases including Crohn disease, ulcerative colitis (UC), rheumatoid arthritis (RA), type 1 diabetes (T1D), celiac disease (CeD), and psoriasis. We found up to 270-fold genetic enrichment between FTD and RA, up to 160-fold genetic enrichment between FTD and UC, up to 180-fold genetic enrichment between FTD and T1D, and up to 175-fold genetic enrichment between FTD and CeD. In contrast, for CBD and PSP, only 1 of the 6 immune-mediated diseases produced genetic enrichment comparable to that seen for FTD, with up to 150-fold genetic enrichment between CBD and CeD and up to 180-fold enrichment between PSP and RA. Further, we found minimal enrichment between ALS and the immune-mediated diseases tested, with the highest levels of enrichment between ALS and RA (up to 20-fold). For FTD, at a conjunction false discovery rate < 0.05 and after excluding SNPs in linkage disequilibrium, we found that 8 of the 15 identified loci mapped to the human leukocyte antigen (HLA) region on Chromosome (Chr) 6. We also found novel candidate FTD susceptibility loci within LRRK2 (leucine rich repeat kinase 2), TBKBP1 (TBK1 binding protein 1), and PGBD5 (piggyBac transposable element derived 5). Functionally, we found that the expression of FTD-immune pleiotropic genes (particularly within the HLA region) is altered in postmortem brain tissue from patients with FTD and is enriched in microglia/macrophages compared to other central nervous system cell types. The main study limitation is that the results represent only clinically diagnosed individuals. Also, given the complex interconnectedness of the HLA region, we were not able to define the specific gene or genes on Chr 6 responsible for our pleiotropic signal. CONCLUSIONS: We show immune-mediated genetic enrichment specifically in FTD, particularly within the HLA region. Our genetic results suggest that for a subset of patients, immune dysfunction may contribute to FTD risk. These findings have potential implications for clinical trials targeting immune dysfunction in patients with FTD