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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]

For the rendering of multiple scattering effects in participating media, methods based on the diffusion approximation are an extremely efficient alternative to Monte Carlo path tracing. However, in sufficiently transparent regions, classical diffusion approximation suffers from non-physical radiative fluxes which leads to a poor match to correct light transport. In particular, this prevents the application of classical diffusion approximation to heterogeneous media, where opaque material is embedded within transparent regions. To address this limitation, we introduce flux-limited diffusion, a technique from the astrophysics domain. This method provides a better approximation to light transport than classical diffusion approximation, particularly when applied to heterogeneous media, and hence broadens the applicability of diffusion-based techniques. We provide an algorithm for flux-limited diffusion, which is validated using the transport theory for a point light source in an infinite homogeneous medium. We further demonstrate that our implementation of flux-limited diffusion produces more accurate renderings of multiple scattering in various heterogeneous datasets than classical diffusion approximation, by comparing both methods to ground truth renderings obtained via volumetric path tracing. [ABSTRACT FROM AUTHOR]

The comparison of molecular surface attributes is of interest for computer aided drug design and the analysis of biochemical simulations. Due to the non-rigid nature of molecular surfaces, partial shape matching is feasible for mapping two surfaces onto each other. We present a novel technique to obtain a mapping relation between two surfaces using a deformable model approach. This relation is used for pair-wise comparison of local surface attributes (e.g. electrostatic potential). We combine the difference value as well as the comparability as derived from the local matching quality in a 3D molecular visualization by mapping them to color. A 2D matrix shows the global dissimilarity in an overview of different data sets in an ensemble. We apply our visualizations to simulation results provided by collaborators from the field of biochemistry to evaluate the effectiveness of our results. [ABSTRACT FROM AUTHOR]

We present a coordinated-view application for the analysis of molecular surface features like cavities, channels and pockets. Our tool employs object-space ambient occlusion for the detection of such features and tracks them over time. It offers time-dependent graphs of metrics concerning those features and allows analyzing the temporal relationship of the features, i.e. when they (dis)appear, split or merge and which features participate in each of these events. The automated analysis process is performed in real time while the user interactively explores a dynamic data set. The system supports linking and brushing to allow for a user-guided visual analysis based on different aspects of the data. We demonstrate the effectiveness of our approach by applying it to data sets from biochemistry and report the insights that can be gained. We also evaluate the benefits of our method with respect to recent advancements in the field. The algorithmic pipeline leverages the computing power of modern GPUs, thus achieving interactive frame rates without any precomputation for fully dynamic data sets. [ABSTRACT FROM AUTHOR]

In common with most infrastructure systems, sewers are often inspected visually. Currently, the results from these inspections inform decisions for significant investments regarding sewer rehabilitation or replacement. In practice, the quality of the data and its analysis are not questioned although psychological research indicates that, as a consequence of the use of subjective analysis of the collected images, errors are inevitable. This article assesses the quality of the analysis of visual sewer inspection data by analysing data reproducibility; three types of capabilities to subjectively assess data are distinguished: the recognition of defects, the description of defects according to a prescribed coding system and the interpretation of sewer inspection reports. The introduced uncertainty is studied using three types of data: inspector examination results of sewer inspection courses, data gathered in day-to-day practice, and the results of repetitive interpretation of the inspection results. After a thorough analysis of the data it can be concluded that for all cases visual sewer inspection data proved poorly reproducible. For the recognition of defects, it was found that the probability of a false positive is in the order of a few percent, the probability of a false negative is in the order of 25%. [ABSTRACT FROM AUTHOR]

The role of innate cells and their receptors within the male genital tract remains poorly understood. Much less is known about the relative contribution of different genital tract cells such as epithelial/stromal cells and resident leucocytes. In this study, we examined innate immune responses to Chlamydia trachomatis by prostate epithelial/stromal cells and prostate resident leucocytes. Murine prostate primary cultures were performed and leucocyte and epithelial/stromal cells were sorted based on surface protein expression of CD45 by magnetism-activated cell sorting or fluorescence-activated cell sorting. Prostate derived CD45- and CD45+ cells were infected with C. trachomatis and chemokine secretion assayed by ELISA. Similar experiments were performed using prostate CD45+ and CD45- cells from myeloid differentiation factor 88 (Myd88-/-) mice or toll-like receptor (Tlr2-/-) and Tlr4mutant double-deficient mice. Moreover, a TLR-signalling pathway array was used to screen changes in different genes involved in TLR-signalling pathways by real-time PCR. Prostate derived CD45- and CD45+ cells responded to chlamydial infection with the production of different chemokines. Both populations expressed genes involved in TLR signalling and required to respond to pathogen-associated molecular patterns and to C. trachomatis infection. Both populations required the adaptor molecule MYD88 to elicit chemokine response against C. trachomatis. TLR2-TLR4 was essential for chemokine production by CD45+ prostate derived cells, but in their absence, CD45- cells still produced significant levels of chemokines.We demonstrate that C. trachomatis is differentially recognised by prostate derived CD45+ and CD45- cells and suggest that diverse strategies are taking place in the local microenvironment of the host in response to the infection. [ABSTRACT FROM AUTHOR]

We present a novel application for the interactive exploration of cavities within proteins in dynamic data sets. Inside a protein, cavities can often be found close to the active center. Therefore, when analyzing a molecular dynamics simulation trajectory it is of great interest to find these cavities and determine if such a cavity opens up to the environment, making the binding site accessible to the surrounding substrate. Our user-driven approach enables expert users to select a certain cavity and track its evolution over time. The user is supported by different visualizations of the extracted cavity to facilitate the analysis. The boundary of the protein and its cavities is obtained by means of volume ray casting, where the volume is computed in real-time for each frame, therefore allowing the examination of time-dependent data sets. A fast, partial segmentation of the volume is applied to obtain the selected cavity and trace it over time. Domain experts found our method useful when they applied it exemplarily on two trajectories of lipases from Rhizomucor miehei and Candida antarctica. In both data sets cavities near the active center were easily identified and tracked over time until they reached the surface and formed an open substrate channel. [ABSTRACT FROM AUTHOR]

The parallel vectors (PV) operator is a feature extraction approach for defining line-type features such as creases (ridges and valleys) in scalar fields, as well as separation, attachment, and vortex core lines in vector fields. In this work, we extend PV feature extraction to higher-order data represented by piecewise analytical functions defined over grid cells. The extraction uses PV in two distinct stages. First, seed points on the feature lines are placed by evaluating the inclusion form of the PV criterion with reduced affine arithmetic. Second, a feature flow field is derived from the higher-order PV expression where the features can be extracted as streamlines starting at the seeds. Our approach allows for guaranteed bounds regarding accuracy with respect to existence, position, and topology of the features obtained. The method is suitable for parallel implementation and we present results obtained with our GPU-based prototype. We apply our method to higher-order data obtained from discontinuous Galerkin fluid simulations. [ABSTRACT FROM AUTHOR]

We propose a novel vortex core line extraction method based on the λ2 vortex region criterion in order to improve the detection of vortex features for 3D flow visualization. The core line is defined as a curve that connects λ2 minima restricted to planes that are perpendicular to the core line. The basic algorithm consists of the following stages: (1) λ2 field construction and isosurface extraction; (2) computation of the curve skeleton of the λ2 isosurface to build an initial prediction for the core line; (3) correction of the locations of the prediction by searching for λ2 minima on planes perpendicular to the core line. In particular, we consider the topology of the vortex core lines, guaranteeing the same topology as the initial curve skeleton. Furthermore, we propose a geometry-guided definition of vortex bifurcation, which represents the split of one core line into two parts. Finally, we introduce a user-guided approach in order to narrow down vortical regions taking into account the graph of λ2 along the computed vortex core line. We demonstrate the effectiveness of our method by comparing our results to previous core line detection methods with both simulated and experimental data; in particular, we show robustness of our method for noise-affected data. [ABSTRACT FROM AUTHOR]

A current research topic in molecular thermodynamics is the condensation of vapor to liquid and the investigation of this process at the molecular level. Condensation is found in many physical phenomena, e.g. the formation of atmospheric clouds or the processes inside steam turbines, where a detailed knowledge of the dynamics of condensation processes will help to optimize energy efficiency and avoid problems with droplets of macroscopic size. The key properties of these processes are the nucleation rate and the critical cluster size. For the calculation of these properties it is essential to make use of a meaningful definition of molecular clusters, which currently is a not completely resolved issue. In this paper a framework capable of interactively visualizing molecular datasets of such nucleation simulations is presented, with an emphasis on the detected molecular clusters. To check the quality of the results of the cluster detection, our framework introduces the concept of flow groups to highlight potential cluster evolution over time which is not detected by the employed algorithm. To confirm the findings of the visual analysis, we coupled the rendering view with a schematic view of the clusters' evolution. This allows to rapidly assess the quality of the molecular cluster detection algorithm and to identify locations in the simulation data in space as well as in time where the cluster detection fails. Thus, thermodynamics researchers can eliminate weaknesses in their cluster detection algorithms. Several examples for the effective and efficient usage of our tool are presented. [ABSTRACT FROM AUTHOR]

In February 2002 an Austrian benchmarking project was completed. The present paper reports on the part of the project dealing with benchmarking of sewerage systems, with a focus on the analysis of investment costs of 34 sewerage system projects. The paper explains the methodology used to make the investment costs of the projects comparable. This was based on an analysis of the final accounts of the finished projects. The paper further delineates the results of the project and considers in detail the important influence of unquantifiable factors, such as economic fluctuations and tendering strategies of the successful contractors, on the calculation of the construction costs. [ABSTRACT FROM AUTHOR]

Health behavior interventions are often grounded in Social Cognitive Theory, but instruments used to assess self-efficacy rely on verbal skills and yield scores that are highly positively skewed. Based on a review of the research literature and qualitative research with key informants, a pictographic medication adherence self-efficacy scale was developed. Two studies were conducted to test the pictographic and color visual analogue scale for assessing self-efficacy for medication adherence. Study 1 (N = 81) demonstrated that the pictographic self-efficacy scale was internally consistent (alpha = 0.68), time stable (2-week test-re-test r = 0.63), and showed evidence for convergent and divergent construct validity. Study 2 (N = 64) further supported the reliability of the pictographic self-efficacy scale with additional data supporting its convergent, divergent and criterion-related validity, including associations with medication adherence and HIV viral load. Distributions of self-efficacy scores approximated normal. This newly developed pictographic scale may be useful in assessing medication adherence self-efficacy in lower-literacy populations. [ABSTRACT FROM AUTHOR]

In this paper we discuss different approaches to generate cutaway illustrations. The purpose of such a drawingis to allow the viewer to have a look into an otherwise solid opaque object. Traditional methods to draw thesekinds of illustrations are evaluated to extract a small and effective set of rules for a computer-based renderingof cutaway illustrations. We show that our approaches are not limited to a specific rendering style but can besuccessfully combined with a great variety of well-known artistic or technical illustration techniques. All methodsof this paper make use of modern graphics hardware functionality to achieve interactive frame rates. [ABSTRACT FROM AUTHOR]

Describes how technical illustrations containing opaque and non-opaque objects can be automatically generated. Traditional methods to show transparency in manual drawings; Information on a proposed hardware-accelerated depth sorting algorithm in image-space; Ways to enhance the visual perception of technical illustrations.