3,883 research outputs found

    Demyelination and axonal preservation in a transgenic mouse model of Pelizaeus-Merzbacher disease

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    It is widely thought that demyelination contributes to the degeneration of axons and, in combination with acute inflammatory injury, is responsible for progressive axonal loss and persistent clinical disability in inflammatory demyelinating disease. In this study we sought to characterize the relationship between demyelination, inflammation and axonal transport changes using a Plp1-transgenic mouse model of Pelizaeus-Merzbacher disease. In the optic pathway of this non-immune mediated model of demyelination, myelin loss progresses from the optic nerve head towards the brain, over a period of months. Axonal transport is functionally perturbed at sites associated with local inflammation and 'damaged' myelin. Surprisingly, where demyelination is complete, naked axons appear well preserved despite a significant reduction of axonal transport. Our results suggest that neuroinflammation and/or oligodendrocyte dysfunction are more deleterious for axonal health than demyelination per se, at least in the short ter

    The Black Hole Mass of NGC 4151. II. Stellar Dynamical Measurement from Near-Infrared Integral Field Spectroscopy

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    We present a revised measurement of the mass of the central black hole (Mbh) in the Seyfert 1 galaxy NGC 4151. The new stellar dynamical mass measurement is derived by applying an axisymmetric orbit-superposition code to near-infrared integral field data obtained using adaptive optics with the Gemini NIFS spectrograph. When our models attempt to fit both the NIFS kinematics and additional low spatial resolution kinematics, our results depend sensitively on how chi-squared is computed--probably a consequence of complex bar kinematics that manifest immediately outside the nuclear region. The most robust results are obtained when only the high spatial resolution kinematic constraints in the nuclear region are included in the fit. Our best estimates for the BH mass and H-band mass-to-light ratio are Mbh~(3.76+/-1.15)E7 Msun (1-sigma error) and M/L(H-band)~0.34+/-0.03 Msun/Lsun (3-sigma error), respectively (the quoted errors reflect the model uncertainties). Our BH mass measurement is consistent with estimates from both reverberation mapping (3.57[+0.45/-0.37]E7 Msun) and gas kinematics (3.0[+0.75/-2.2]E7 Msun; 1-sigma errors), and our best-fit mass-to-light ratio is consistent with the photometric estimate of M/L(H-band)=0.4+/-0.2 Msun/Lsun. The NIFS kinematics give a central bulge velocity dispersion sigma_c=116+/-3 km/s, bringing this object slightly closer to the M-sigma relation for quiescent galaxies. Although NGC 4151 is one of only a few Seyfert 1 galaxies in which it is possible to obtain a direct dynamical BH mass measurement--and thus, an independent calibration of the reverberation mapping mass scale--the complex bar kinematics makes it less than ideally suited for this purpose.Comment: 21 pages, 15 figures. Accepted for publication in Ap

    Label-efficient Contrastive Learning-based model for nuclei detection and classification in 3D Cardiovascular Immunofluorescent Images

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    Recently, deep learning-based methods achieved promising performance in nuclei detection and classification applications. However, training deep learning-based methods requires a large amount of pixel-wise annotated data, which is time-consuming and labor-intensive, especially in 3D images. An alternative approach is to adapt weak-annotation methods, such as labeling each nucleus with a point, but this method does not extend from 2D histopathology images (for which it was originally developed) to 3D immunofluorescent images. The reason is that 3D images contain multiple channels (z-axis) for nuclei and different markers separately, which makes training using point annotations difficult. To address this challenge, we propose the Label-efficient Contrastive learning-based (LECL) model to detect and classify various types of nuclei in 3D immunofluorescent images. Previous methods use Maximum Intensity Projection (MIP) to convert immunofluorescent images with multiple slices to 2D images, which can cause signals from different z-stacks to falsely appear associated with each other. To overcome this, we devised an Extended Maximum Intensity Projection (EMIP) approach that addresses issues using MIP. Furthermore, we performed a Supervised Contrastive Learning (SCL) approach for weakly supervised settings. We conducted experiments on cardiovascular datasets and found that our proposed framework is effective and efficient in detecting and classifying various types of nuclei in 3D immunofluorescent images.Comment: 11 pages, 5 figures, MICCAI Workshop Conference 202

    Discovery and Early Evolution of ASASSN-19bt, the First TDE Detected by TESS

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    We present the discovery and early evolution of ASASSN-19bt, a tidal disruption event (TDE) discovered by the All-Sky Automated Survey for Supernovae (ASAS-SN) at a distance of d115d\simeq115 Mpc and the first TDE to be detected by TESS. As the TDE is located in the TESS Continuous Viewing Zone, our dataset includes 30-minute cadence observations starting on 2018 July 25, and we precisely measure that the TDE begins to brighten 8.3\sim8.3 days before its discovery. Our dataset also includes 18 epochs of Swift UVOT and XRT observations, 2 epochs of XMM-Newton observations, 13 spectroscopic observations, and ground data from the Las Cumbres Observatory telescope network, spanning from 32 days before peak through 37 days after peak. ASASSN-19bt thus has the most detailed pre-peak dataset for any TDE. The TESS light curve indicates that the transient began to brighten on 2019 January 21.6 and that for the first 15 days its rise was consistent with a flux t2\propto t^2 power-law model. The optical/UV emission is well-fit by a blackbody SED, and ASASSN-19bt exhibits an early spike in its luminosity and temperature roughly 32 rest-frame days before peak and spanning up to 14 days that has not been seen in other TDEs, possibly because UV observations were not triggered early enough to detect it. It peaked on 2019 March 04.9 at a luminosity of L1.3×1044L\simeq1.3\times10^{44} ergs s1^{-1} and radiated E3.2×1050E\simeq3.2\times10^{50} ergs during the 41-day rise to peak. X-ray observations after peak indicate a softening of the hard X-ray emission prior to peak, reminiscent of the hard/soft states in X-ray binaries.Comment: 23 pages, 14 figures, 5 tables. A machine-readable table containing the host-subtracted photometry presented in this manuscript is included as an ancillary fil

    Application of an Equilibrium Vaporization Model to the Ablation of Chondritic and Achondritic Meteoroids

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    We modeled equilibrium vaporization of chondritic and achondritic materials using the MAGMA code. We calculated both instantaneous and integrated element abundances of Na, Mg, Ca, Al, Fe, Si, Ti, and K in chondritic and achondritic meteors. Our results are qualitatively consistent with observations of meteor spectra.Comment: 8 pages, 4 figures; in press, Earth, Moon, and Planets, Meteoroids 2004 conference proceeding

    Local cortical dynamics of burst suppression in the anaesthetized brain

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    Burst suppression is an electroencephalogram pattern that consists of a quasi-periodic alternation between isoelectric ‘suppressions’ lasting seconds or minutes, and high-voltage ‘bursts’. It is characteristic of a profoundly inactivated brain, occurring in conditions including hypothermia, deep general anaesthesia, infant encephalopathy and coma. It is also used in neurology as an electrophysiological endpoint in pharmacologically induced coma for brain protection after traumatic injury and during status epilepticus. Classically, burst suppression has been regarded as a ‘global’ state with synchronous activity throughout cortex. This assumption has influenced the clinical use of burst suppression as a way to broadly reduce neural activity. However, the extent of spatial homogeneity has not been fully explored due to the challenges in recording from multiple cortical sites simultaneously. The neurophysiological dynamics of large-scale cortical circuits during burst suppression are therefore not well understood. To address this question, we recorded intracranial electrocorticograms from patients who entered burst suppression while receiving propofol general anaesthesia. The electrodes were broadly distributed across cortex, enabling us to examine both the dynamics of burst suppression within local cortical regions and larger-scale network interactions. We found that in contrast to previous characterizations, bursts could be substantially asynchronous across the cortex. Furthermore, the state of burst suppression itself could occur in a limited cortical region while other areas exhibited ongoing continuous activity. In addition, we found a complex temporal structure within bursts, which recapitulated the spectral dynamics of the state preceding burst suppression, and evolved throughout the course of a single burst. Our observations imply that local cortical dynamics are not homogeneous, even during significant brain inactivation. Instead, cortical and, implicitly, subcortical circuits express seemingly different sensitivities to high doses of anaesthetics that suggest a hierarchy governing how the brain enters burst suppression, and emphasize the role of local dynamics in what has previously been regarded as a global state. These findings suggest a conceptual shift in how neurologists could assess the brain function of patients undergoing burst suppression. First, analysing spatial variation in burst suppression could provide insight into the circuit dysfunction underlying a given pathology, and could improve monitoring of medically-induced coma. Second, analysing the temporal dynamics within a burst could help assess the underlying brain state. This approach could be explored as a prognostic tool for recovery from coma, and for guiding treatment of status epilepticus. Overall, these results suggest new research directions and methods that could improve patient monitoring in clinical practice.Burroughs Wellcome Fund (Career Award at the Scientific Interface)National Institutes of Health (U.S.) (Director's Pioneer Award DP10D003646)National Institutes of Health (U.S.) (Transformative 1R01GM104948

    People with aphasia’s perspectives of the therapeutic alliance during speech-language intervention: A Q methodological approach

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    Purpose: To identify which elements of the therapeutic alliance are important to people with aphasia (PWA) attending speech-language pathology post-stroke. Method: A Q methodology design was adopted to explore which elements of the therapeutic alliance were valued by PWA. Statements (n = 453) relevant to the research question were extrapolated from the literature and qualitative interviews. A representative sample of statements (n = 38) was identified from the expansive data set. PWA (n = 23) sorted statements hierarchically according to whether they thought the statement was important or unimportant. Completed Q sorts were analysed using a by-person factor analysis. Result: Analysis yielded a five-factor solution, representing five distinct viewpoints: (1) acknowledge me, help me to understand; (2) respect me, listen to me; (3) challenge me, direct me; (4) understand me, laugh with me; and (5) hear me, encourage me. Conclusion: The findings highlight the need for clinicians to adopt a flexible and idiosyncratic approach to therapeutic alliance construction in order to meet the relational needs of a heterogeneous population. This is the first study to use Q methodology with PWA, demonstrating that Q methodology is an effective and viable method for investigating subjectivity in this population
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