Search

BACKGROUND Niemann-Pick disease type C is a rare lysosomal storage disorder. We evaluated the safety and efficacy of N-acetyl-L-leucine (NALL), an agent that potentially ameliorates lysosomal and metabolic dysfunction, for the treatment of Niemann-Pick disease type C. METHODS In this double-blind, placebo-controlled, crossover trial, we randomly assigned patients 4 years of age or older with genetically confirmed Niemann-Pick disease type C in a 1:1 ratio to receive NALL for 12 weeks, followed by placebo for 12 weeks, or to receive placebo for 12 weeks, followed by NALL for 12 weeks. NALL or matching placebo was administered orally two to three times per day, with patients 4 to 12 years of age receiving weight-based doses (2 to 4 g per day) and those 13 years of age or older receiving a dose of 4 g per day. The primary end point was the total score on the Scale for the Assessment and Rating of Ataxia (SARA; range, 0 to 40, with lower scores indicating better neurologic status). Secondary end points included scores on the Clinical Global Impression of Improvement, the Spinocerebellar Ataxia Functional Index, and the Modified Disability Rating Scale. Crossover data from the two 12-week periods in each group were included in the comparisons of NALL with placebo. RESULTS A total of 60 patients 5 to 67 years of age were enrolled. The mean baseline SARA total scores used in the primary analysis were 15.88 before receipt of the first dose of NALL (60 patients) and 15.68 before receipt of the first dose of placebo (59 patients; 1 patient never received placebo). The mean (±SD) change from baseline in the SARA total score was -1.97±2.43 points after 12 weeks of receiving NALL and -0.60±2.39 points after 12 weeks of receiving placebo (least-squares mean difference, -1.28 points; 95% confidence interval, -1.91 to -0.65; P<0.001). The results for the secondary end points were generally supportive of the findings in the primary analysis, but these were not adjusted for multiple comparisons. The incidence of adverse events was similar with NALL and placebo, and no treatment-related serious adverse events occurred. CONCLUSIONS Among patients with Niemann-Pick disease type C, treatment with NALL for 12 weeks led to better neurologic status than placebo. A longer period is needed to determine the long-term effects of this agent in patients with Niemann-Pick disease type C. (Funded by IntraBio; ClinicalTrials.gov number, NCT05163288; EudraCT number, 2021-005356-10.) [ABSTRACT FROM AUTHOR]

Six binary-merger progenitors of supernova 1987A (SN 1987A) with properties close to those of the blue supergiant Sanduleak −69°202 are exploded by neutrino heating and evolved until long after shock breakout in 3D and continued for light-curve calculations in spherical symmetry. Our results confirm previous findings for single-star progenitors: (1) 3D neutrino-driven explosions with SN 1987A-like energies synthesize 56Ni masses consistent with the radioactive light-curve tail; (2) hydrodynamic models mix hydrogen inward to minimum velocities below 40 km s−1 compatible with spectral observations of SN 1987A; and (3) for given explosion energy the efficiency of outward radioactive 56Ni mixing depends mainly on high growth factors of Rayleigh–Taylor instabilities at the (C+O)/He and He/H composition interfaces and a weak interaction of fast plumes with the reverse shock occurring below the He/H interface. All binary-merger models possess presupernova radii matching the photometric radius of Sanduleak −69°202 and a structure of the outer layers allowing them to reproduce the observed initial luminosity peak in the first ∼7 days. Models that mix about 0.5 M⊙ of hydrogen into the He-shell and exhibit strong outward mixing of 56Ni with maximum velocities exceeding the 3000 km s−1 observed for the bulk of ejected 56Ni have light-curve shapes in good agreement with the dome of the SN 1987A light curve. A comparative analysis of the best representatives of our 3D neutrino-driven explosion models of SN 1987A based on single-star and binary-merger progenitors reveals that only one binary model fulfills all observational constraints, except one. [ABSTRACT FROM AUTHOR]

We present 3D full-sphere supernova simulations of non-rotating low-mass (∼9 M⊙) progenitors, covering the entire evolution from core collapse through bounce and shock revival, through shock breakout from the stellar surface, until fallback is completed several days later. We obtain low-energy explosions (∼0.5–1.0 × 1050 erg) of iron-core progenitors at the low-mass end of the core-collapse supernova (LMCCSN) domain and compare to a super-AGB (sAGB) progenitor with an oxygen–neon–magnesium core that collapses and explodes as electron-capture supernova (ECSN). The onset of the explosion in the LMCCSN models is modelled self-consistently using the vertex-prometheus code, whereas the ECSN explosion is modelled using parametric neutrino transport in the prometheus-HOTB code, choosing different explosion energies in the range of previous self-consistent models. The sAGB and LMCCSN progenitors that share structural similarities have almost spherical explosions with little metal mixing into the hydrogen envelope. A LMCCSN with less second dredge-up results in a highly asymmetric explosion. It shows efficient mixing and dramatic shock deceleration in the extended hydrogen envelope. Both properties allow fast nickel plumes to catch up with the shock, leading to extreme shock deformation and aspherical shock breakout. Fallback masses of |$\mathord {\lesssim }\, 5\, \mathord {\times }\, 10^{-3}$|  M⊙ have no significant effects on the neutron star (NS) masses and kicks. The anisotropic fallback carries considerable angular momentum, however, and determines the spin of the newly born NS. The LMCCSN model with less second dredge-up results in a hydrodynamic and neutrino-induced NS kick of >40 km s−1 and a NS spin period of ∼30 ms, both not largely different from those of the Crab pulsar at birth. [ABSTRACT FROM AUTHOR]

It is widely accepted that partial nitrification by ANAMMOX has the potential to become one of the key processes in wastewater treatment. However, large greenhouse gas emissions have been panobserved in many cases. A novel mesh separated reactor, developed to allow continuous operation of deammonification at smaller scale without external biomass selection, was compared to a conventional single-chamber deammonification sequencing batch reactor (SBR), where both were equally-sized pilot-scale reactors. The mesh reactor consisted of an aerated and an anoxic zone separated by a mesh. The resulting differences in the structure of the microbial community were detected by next-generation sequencing. When both systems were operated in a sequencing batch mode, both systems had comparable nitrous oxide emission factors in the range of 4% to 5% of the influent nitrogen load. A significant decrease was observed after switching from sequencing batch mode to continuous operation. [ABSTRACT FROM AUTHOR]

A large fraction of core-collapse supernovae (CCSNe), 30-50 per cent, are expected to originate from the low-mass end of progenitors with MZAMS = 8-12☉. However, degeneracy effects make stellar evolution modelling of such stars challenging, and few predictions for their supernova light curves and spectra have been presented. Here, we calculate synthetic nebular spectra of a 9☉ Fe CCSN model exploded with the neutrino mechanism. The model predicts emission lines with FWHM ∼ 1000 km s-1, including signatures from each deep layer in the metal core.We compare this model to the observations of the three subluminous IIP SNe with published nebular spectra; SN 1997D, SN 2005cs and SN 2008bk. The predictions of both line profiles and luminosities are in good agreement with SN 1997D and SN 2008bk. The close fit of a model with no tuning parameters provides strong evidence for an association of these objects with low-mass Fe CCSNe. For SN 2005cs, the interpretation is less clear, as the observational coverage ended before key diagnostic lines from the core had emerged. We perform a parametrized study of the amount of explosively made stable nickel, and find that none of these three SNe show the high 58Ni/56Ni ratio predicted by current models of electron capture SNe (ECSNe) and ECSN-like explosions. Combined with clear detection of lines from O and He shell material, these SNe rather originate from Fe core progenitors. We argue that the outcome of self-consistent explosion simulations of low-mass stars, which gives fits to many key observables, strongly suggests that the class of subluminous Type IIP SNe is the observational counterpart of the lowest mass CCSNe. [ABSTRACT FROM AUTHOR]

We present an approach to adaptively select time steps from time-dependent volume data sets for an integrated and comprehensive visualization. This reduced set of time steps not only saves cost, but also allows to show both the spatial structure and temporal development in one combined rendering. Our selection optimizes the coverage of the complete data on the basis of a minimum-cost flow-based technique to determine meaningful distances between time steps. As both optimal solutions of the involved transport and selection problem are prohibitively expensive, we present new approaches that are significantly faster with only minor deviations. We further propose an adaptive scheme for the progressive incorporation of new time steps. An interactive volume raycaster produces an integrated rendering of the selected time steps, and their computed differences are visualized in a dedicated chart to provide additional temporal similarity information. We illustrate and discuss the utility of our approach by means of different data sets from measurements and simulation. [ABSTRACT FROM AUTHOR]

This survey provides an introduction into eye tracking visualization with an overview of existing techniques. Eye tracking is important for evaluating user behaviour. Analysing eye tracking data is typically done quantitatively, applying statistical methods. However, in recent years, researchers have been increasingly using qualitative and exploratory analysis methods based on visualization techniques. For this state-of-the-art report, we investigated about 110 research papers presenting visualization techniques for eye tracking data. We classified these visualization techniques and identified two main categories: point-based methods and methods based on areas of interest. Additionally, we conducted an expert review asking leading eye tracking experts how they apply visualization techniques in their analysis of eye tracking data. Based on the experts' feedback, we identified challenges that have to be tackled in the future so that visualizations will become even more widely applied in eye tracking research. [ABSTRACT FROM AUTHOR]

In this report, we review the current state of the art of web-based visualization applications. Recently, an increasing number of web-based visualization applications have emerged. This is due to the fact that new technologies offered by modern browsers greatly increased the capabilities for visualizations on the web. We first review these technical aspects that are enabling this development. This includes not only improvements for local rendering like WebGL and HTML5, but also infrastructures like grid or cloud computing platforms. Another important factor is the transfer of data between the server and the client. Therefore, we also discuss advances in this field, for example methods to reduce bandwidth requirements like compression and other optimizations such as progressive rendering and streaming. After establishing these technical foundations, we review existing web-based visualization applications and prototypes from various application domains. Furthermore, we propose a classification of these web-based applications based on the technologies and algorithms they employ. Finally, we also discuss promising application areas that would benefit from web-based visualization and assess their feasibility based on the existing approaches. [ABSTRACT FROM AUTHOR]

In many disciplines, such as computer aided drug design, multiple simulation runs are performed with varying parameters, yielding ensembles of data sets. Comparative visualisation of these simulation results can help understanding the influence different parameters have. However, researchers might need to compare large numbers of variants. Single desktop monitors often do not have the resolution and screen size required for showing a whole ensemble at once with sufficient detail. Wall-sized high-resolution displays can be a solution for this problem. Although a number of studies has been conducted on how large high-resolution displays affect the speed and accuracy of certain tasks, only few of them are related to actual scientific visualisation tasks. We built a system for comparative visualisation of simulation results that can be used with conventional desktop monitors and with large high-resolution displays. We conducted a study using biochemical simulation data to evaluate the impact of screen size and 3D stereo output on a comparison task. [ABSTRACT FROM AUTHOR]

We present a novel physically-based method to visualize stress tensor fields. By incorporating photoelasticity into traditional raycasting and extending it with reflection and refraction, taking into account polarization, we obtain the virtual counterpart to traditional experimental polariscopes. This allows us to provide photoelastic analysis of stress tensor fields in arbitrary domains. In our model, the optical material properties, such as stress-optic coefficient and refractive index, can either be chosen in compliance with the subject under investigation, or, in case of stress problems that do not model optical properties or that are not transparent, be chosen according to known or even new transparent materials. This enables direct application of established polariscope methodology together with respective interpretation. Using a GPU-based implementation, we compare our technique to experimental data, and demonstrate its utility with several simulated datasets. [ABSTRACT FROM AUTHOR]