Dark Matter in the Dwarf Galaxy NGC 247

Dwarf galaxies are dominated by dark matter even in the innermost regions and, therefore, provide excellent probes for the investigation of dark halos. To that purpose, we analyse ROSAT PSPC-data of the dwarf galaxy NGC 247. We focus in particular on the diffuse X-ray emission in the $1/4$keV band. Assuming an isothermal density profile, we find that the mass of the hot emitting gas is about $10^8 {\rm M_{\odot}}$, corresponding to $\lesssim 0.5$ of the total dynamical mass of the galaxy. The total mass of NGC 247, as derived from the X-ray data agrees quite well with the value obtained from the measured rotation curve (Burlak). The X-ray profile in the $3/4$keV and $1.5$keV band shows an excess at a radial distance of about $15$ arcmin from the center. Such a ``hump'' in the radial X-ray profile can be explained by the presence of a cluster of young low mass stars or brown dwarfs. Therefore, NGC 247 offers the possibility to observe the formation of a halo of MACHOs.Comment: 6 pages, accepted for publication in A &

High-speed multiplane structured illumination microscopy of living cells using an image-splitting prism

Abstract Super-resolution structured illumination microscopy (SR-SIM) can be conducted at video-rate acquisition speeds when combined with high-speed spatial light modulators and sCMOS cameras, rendering it particularly suitable for live-cell imaging. If, however, three-dimensional (3D) information is desired, the sequential acquisition of vertical image stacks employed by current setups significantly slows down the acquisition process. In this work, we present a multiplane approach to SR-SIM that overcomes this slowdown via the simultaneous acquisition of multiple object planes, employing a recently introduced multiplane image splitting prism combined with high-speed SIM illumination. This strategy requires only the introduction of a single optical element and the addition of a second camera to acquire a laterally highly resolved 3D image stack. We demonstrate the performance of multiplane SIM by applying this instrument to imaging the dynamics of mitochondria in living COS-7 cells.urldate: 2020-01-14 file: Full Text:/Users/peter/Zotero/storage/QED2X9HN/Descloux et al. - 2019 - High-speed multiplane structured illumination micr.pdf:application/pdfstatus: publishe

Incidence of Arrhythmias and Myocardial Ischaemia During Haemodialysis and Haemofiltration

Thirty-two patients (10 male, 22 female; age 37-82 years) undergoing maintenance haemodialysis or haemofiltration were studied by means of Holter device capable of simultaneously analysing rhythm and ST changes in three leads. Twenty-five patients were on haemodialysis, seven on haemofiltration, mean duration of haemodialysis/haemofiltration being 3.4±3 years. Incidence of ventricular tachycardia was low, being detected only in 1 of 32 patients. Ventricular premature beats in excess of 10/h during a period of 2 h were found in 8 of 32 patients and 100 supraventricular premature beats for 2 h or more in 4 of 32 patients. Both ventricular premature beats and supraventricular premature beats were most frequently recorded during the last hour of haemodialysis/haemofiltration. ECG signs of ischaemia were detected in eight patients, four of whom were asymptomatic. Ischaemia also occurred predominantly during the last hour of haemodialysis/haemofiltration. Two symptomatic patients displayed neither arrhythmias nor ST-changes while being monitored. The study shows that silent ischaemia and arrhythmias in patients under going chronic haemodialysis/haemofiltration may not be infrequent. Recognition of these events could be of importance in the management of these patient

Bayesian Networks for Max-linear Models

We study Bayesian networks based on max-linear structural equations as introduced in Gissibl and Kl\"uppelberg [16] and provide a summary of their independence properties. In particular we emphasize that distributions for such networks are generally not faithful to the independence model determined by their associated directed acyclic graph. In addition, we consider some of the basic issues of estimation and discuss generalized maximum likelihood estimation of the coefficients, using the concept of a generalized likelihood ratio for non-dominated families as introduced by Kiefer and Wolfowitz [21]. Finally we argue that the structure of a minimal network asymptotically can be identified completely from observational data.Comment: 18 page

Ecological resilience in lakes and the conjunction fallacy

There is a pressing need to apply stability and resilience theory to environmental management to restore degraded ecosystems effectively and to mitigate the effects of impending environmental change. Lakes represent excellent model case studies in this respect and have been used widely to demonstrate theories of ecological stability and resilience that are needed to underpin preventative management approaches. However, we argue that this approach is not yet fully developed because the pursuit of empirical evidence to underpin such theoretically grounded management continues in the absence of an objective probability framework. This has blurred the lines between intuitive logic (based on the elementary principles of probability) and extensional logic (based on assumption and belief) in this field

PatientExploreR: an extensible application for dynamic visualization of patient clinical history from electronic health records in the OMOP common data model.

MotivationElectronic health records (EHRs) are quickly becoming omnipresent in healthcare, but interoperability issues and technical demands limit their use for biomedical and clinical research. Interactive and flexible software that interfaces directly with EHR data structured around a common data model (CDM) could accelerate more EHR-based research by making the data more accessible to researchers who lack computational expertise and/or domain knowledge.ResultsWe present PatientExploreR, an extensible application built on the R/Shiny framework that interfaces with a relational database of EHR data in the Observational Medical Outcomes Partnership CDM format. PatientExploreR produces patient-level interactive and dynamic reports and facilitates visualization of clinical data without any programming required. It allows researchers to easily construct and export patient cohorts from the EHR for analysis with other software. This application could enable easier exploration of patient-level data for physicians and researchers. PatientExploreR can incorporate EHR data from any institution that employs the CDM for users with approved access. The software code is free and open source under the MIT license, enabling institutions to install and users to expand and modify the application for their own purposes.Availability and implementationPatientExploreR can be freely obtained from GitHub: https://github.com/BenGlicksberg/PatientExploreR. We provide instructions for how researchers with approved access to their institutional EHR can use this package. We also release an open sandbox server of synthesized patient data for users without EHR access to explore: http://patientexplorer.ucsf.edu.Supplementary informationSupplementary data are available at Bioinformatics online

The Relationship between Fenestrations, Sieve Plates and Rafts in Liver Sinusoidal Endothelial Cells

Fenestrations are transcellular pores in endothelial cells that facilitate transfer of substrates between blood and the extravascular compartment. In order to understand the regulation and formation of fenestrations, the relationship between membrane rafts and fenestrations was investigated in liver sinusoidal endothelial cells where fenestrations are grouped into sieve plates. Three dimensional structured illumination microscopy, scanning electron microscopy, internal reflectance fluorescence microscopy and two-photon fluorescence microscopy were used to study liver sinusoidal endothelial cells isolated from mice. There was an inverse distribution between sieve plates and membrane rafts visualized by structured illumination microscopy and the fluorescent raft stain, Bodipy FL C5 ganglioside GM1. 7-ketocholesterol and/or cytochalasin D increased both fenestrations and lipid-disordered membrane, while Triton X-100 decreased both fenestrations and lipid-disordered membrane. The effects of cytochalasin D on fenestrations were abrogated by co-administration of Triton X-100, suggesting that actin disruption increases fenestrations by its effects on membrane rafts. Vascular endothelial growth factor (VEGF) depleted lipid-ordered membrane and increased fenestrations. The results are consistent with a sieve-raft interaction, where fenestrations form in non-raft lipid-disordered regions of endothelial cells once the membrane-stabilizing effects of actin cytoskeleton and membrane rafts are diminished.Full Tex

Subcellular heterogeneity of ryanodine receptor properties in ventricular myocytes with low T-tubule density

Rationale: In ventricular myocytes of large mammals, not all ryanodine receptor (RyR) clusters are associated with T-tubules (TTs); this fraction increases with cellular remodeling after myocardial infarction (MI). Objective: To characterize RyR functional properties in relation to TT proximity, at baseline and after MI. Methods: Myocytes were isolated from left ventricle of healthy pigs (CTRL) or from the area adjacent to a myocardial infarction (MI). Ca2+ transients were measured under whole-cell voltage clamp during confocal linescan imaging (fluo-3) and segmented according to proximity of TTs (sites of early Ca2+ release, F>F50 within 20 ms) or their absence (delayed areas). Spontaneous Ca2+ release events during diastole, Ca2+ sparks, reflecting RyR activity and properties, were subsequently assigned to either category. Results: In CTRL, spark frequency was higher in proximity of TTs, but spark duration was significantly shorter. Block of Na+/Ca2+ exchanger (NCX) prolonged spark duration selectively near TTs, while block of Ca2+ influx via Ca2+ channels did not affect sparks properties. In MI, total spark mass was increased in line with higher SR Ca2+ content. Extremely long sparks (>47.6 ms) occurred more frequently. The fraction of near-TT sparks was reduced; frequency increased mainly in delayed sites. Increased duration was seen in near-TT sparks only; Ca2+ removal by NCX at the membrane was significantly lower in MI. Conclusion: TT proximity modulates RyR cluster properties resulting in intracellular heterogeneity of diastolic spark activity. Remodeling in the area adjacent to MI differentially affects these RyR subpopulations. Reduction of the number of sparks near TTs and reduced local NCX removal limit cellular Ca2+ loss and raise SR Ca2+ content, but may promote Ca2+ waves

The serotonergic central nervous system of the Drosophila larva: anatomy and behavioral function.

The Drosophila larva has turned into a particularly simple model system for studying the neuronal basis of innate behaviors and higher brain functions. Neuronal networks involved in olfaction, gustation, vision and learning and memory have been described during the last decade, often up to the single-cell level. Thus, most of these sensory networks are substantially defined, from the sensory level up to third-order neurons. This is especially true for the olfactory system of the larva. Given the wealth of genetic tools in Drosophila it is now possible to address the question how modulatory systems interfere with sensory systems and affect learning and memory. Here we focus on the serotonergic system that was shown to be involved in mammalian and insect sensory perception as well as learning and memory. Larval studies suggested that the serotonergic system is involved in the modulation of olfaction, feeding, vision and heart rate regulation. In a dual anatomical and behavioral approach we describe the basic anatomy of the larval serotonergic system, down to the single-cell level. In parallel, by expressing apoptosis-inducing genes during embryonic and larval development, we ablate most of the serotonergic neurons within the larval central nervous system. When testing these animals for naïve odor, sugar, salt and light perception, no profound phenotype was detectable; even appetitive and aversive learning was normal. Our results provide the first comprehensive description of the neuronal network of the larval serotonergic system. Moreover, they suggest that serotonin per se is not necessary for any of the behaviors tested. However, our data do not exclude that this system may modulate or fine-tune a wide set of behaviors, similar to its reported function in other insect species or in mammals. Based on our observations and the availability of a wide variety of genetic tools, this issue can now be addressed

An Efficient Workflow for Modelling High-Dimensional Spatial Extremes

A successful model for high-dimensional spatial extremes should, in principle, be able to describe both weakening extremal dependence at increasing levels and changes in the type of extremal dependence class as a function of the distance between locations. Furthermore, the model should allow for computationally tractable inference using inference methods that efficiently extract information from data and that are robust to model misspecification. In this paper, we demonstrate how to fulfil all these requirements by developing a comprehensive methodological workflow for efficient Bayesian modelling of high-dimensional spatial extremes using the spatial conditional extremes model while performing fast inference with R-INLA. We then propose a post hoc adjustment method that results in more robust inference by properly accounting for possible model misspecification. The developed methodology is applied for modelling extreme hourly precipitation from high-resolution radar data in Norway. Inference is computationally efficient, and the resulting model fit successfully captures the main trends in the extremal dependence structure of the data. Robustifying the model fit by adjusting for possible misspecification further improves model performance