An Engineered sgsh Mutant Zebrafish Recapitulates Molecular and Behavioural Pathobiology of Sanfilippo Syndrome A/MPS IIIA

Mucopolysaccharidosis IIIA (MPS IIIA, Sanfilippo syndrome type A), a paediatric neurological lysosomal storage disease, is caused by impaired function of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH) resulting in impaired catabolism of heparan sulfate glycosaminoglycan (HS GAG) and its accumulation in tissues. MPS IIIA represents a significant proportion of childhood dementias. This condition generally leads to patient death in the teenage years, yet no effective therapy exists for MPS IIIA and a complete understanding of the mechanisms of MPS IIIA pathogenesis is lacking. Here, we employ targeted CRISPR/Cas9 mutagenesis to generate a model of MPS IIIA in the zebrafish, a model organism with strong genetic tractability and amenity for high-throughput screening. The sgsh^Δex5−6 zebrafish mutant exhibits a complete absence of Sgsh enzymatic activity, leading to progressive accumulation of HS degradation products with age. sgsh^Δex5−6 zebrafish faithfully recapitulate diverse CNS-specific features of MPS IIIA, including neuronal lysosomal overabundance, complex behavioural phenotypes, and profound, lifelong neuroinflammation. We further demonstrate that neuroinflammation in sgsh^Δex5−6 zebrafish is largely dependent on interleukin-1β and can be attenuated via the pharmacological inhibition of Caspase-1, which partially rescues behavioural abnormalities in sgsh^Δex5−6 mutant larvae in a context-dependent manner. We expect the sgsh^Δex5−6 zebrafish mutant to be a valuable resource in gaining a better understanding of MPS IIIA pathobiology towards the development of timely and effective therapeutic interventions.     

Synchronization in complex networks of phase oscillators: A survey

The emergence of synchronization in a network of coupled oscillators is a fascinating subject of multidisciplinary research. This survey reviews the vast literature on the theory and the applications of complex oscillator networks. We focus on phase oscillator models that are widespread in real-world synchronization phenomena, that generalize the celebrated Kuramoto model, and that feature a rich phenomenology. We review the history and the countless applications of this model throughout science and engineering. We justify the importance of the widespread coupled oscillator model as a locally canonical model and describe some selected applications relevant to control scientists, including vehicle coordination, electric power networks, and clock synchronization. We introduce the reader to several synchronization notions and performance estimates. We propose analysis approaches to phase and frequency synchronization, phase balancing, pattern formation, and partial synchronization. We present the sharpest known results about synchronization in networks of homogeneous and heterogeneous oscillators, with complete or sparse interconnection topologies, and in finite-dimensional and infinite-dimensional settings. We conclude by summarizing the limitations of existing analysis methods and by highlighting some directions for future research.     

pROST: a smoothed \ell _p-norm robust online subspace tracking method for background subtraction in video

An increasing number of methods for background subtraction use Robust PCA to identify sparse foreground objects. While many algorithms use the \(\ell _1\) -norm as a convex relaxation of the ideal sparsifying function, we approach the problem with a smoothed \(\ell _p\) -quasi-norm and present pROST, a method for robust online subspace tracking. The algorithm is based on alternating minimization on manifolds. Implemented on a graphics processing unit, it achieves realtime performance at a resolution of \(160 \times 120\) . Experimental results on a state-of-the-art benchmark for background subtraction on real-world video data indicate that the method succeeds at a broad variety of background subtraction scenarios, and it outperforms competing approaches when video quality is deteriorated by camera jitter.     

Quantifying the evolution of TTCN-3 as a language

Ten years of maintenance, nine published revisions of the standards for the Testing and Test Control Notation version 3 (TTCN-3), more than 500 change requests since 2006, and 10 years of activity on the official TTCN-3 mailing list add up to a rich history, not unlike that of many successful Open Source Software (OSS) projects. In this article, we contemplate TTCN-3 in the context of software evolution and examine its history quantitatively. We mined the changes in the textual content of the standards, the data in change requests from the past 5 years, and the mailing list archives from the past 10 years. In addition, to characterize the use of the TTCN-3 we investigated the meta-data of the contributions at the TTCN-3 User Conference, and the use of language constructs in a large-scale TTCN-3 test suite. Based on these data sets, we first analyze the amount, density, and location of changes within the different parts of the standard. Then, we analyze the activity and focus of the user community and the maintenance team in both the change request management system and the official TTCN-3 mailing list. Finally, we analyze the distribution of contributions at the TTCN-3 User Conference across different topics over the past 8 years and construct use anomalies during the development of a large-scale test suite. Our findings indicate that the TTCN-3 is becoming increasingly stable as the overall change density and intensity, as well as the number of change requests are decreasing, despite the monotonous increase in the size of the standards.     

UR: SMART–A tool for analyzing social media content

Information Systems and e-Business Management - The digital transformation, with its ongoing trend towards electronic business, confronts companies with increasingly growing amounts of data which...     

Influence of motion correction on the visual analysis of cardiac magnetic resonance stress perfusion imaging

Objective

Image post-processing corrects for cardiac and respiratory motion (MoCo) during cardiovascular magnetic resonance (CMR) stress perfusion. The study analyzed its influence on visual image evaluation.

Materials and methods

Sixty-two patients with (suspected) coronary artery disease underwent a standard CMR stress perfusion exam during free-breathing. Image post-processing was performed without (non-MoCo) and with MoCo (image intensity normalization; motion extraction with iterative non-rigid registration; motion warping with the combined displacement field). Images were evaluated regarding the perfusion pattern (perfusion deficit, dark rim artifact, uncertain signal loss, and normal perfusion), the general image quality (non-diagnostic, imperfect, good, and excellent), and the reader’s subjective confidence to assess the images (not confident, confident, very confident).

Results

Fifty-three (non-MoCo) and 52 (MoCo) myocardial segments were rated as ‘perfusion deficit’, 113 vs. 109 as ‘dark rim artifacts’, 9 vs. 7 as ‘uncertain signal loss’, and 817 vs. 824 as ‘normal’. Agreement between non-MoCo and MoCo was high with no diagnostic difference per-patient. The image quality of MoCo was rated more often as ‘good’ or ‘excellent’ (92 vs. 63%), and the diagnostic confidence more often as “very confident” (71 vs. 45%) compared to non-MoCo.

Conclusions

The comparison of perfusion images acquired during free-breathing and post-processed with and without motion correction demonstrated that both methods led to a consistent evaluation of the perfusion pattern, while the image quality and the reader’s subjective confidence to assess the images were rated more favorably for MoCo.

     

Physically Meaningful Rendering using Tristimulus Colours

In photorealistic image synthesis the radiative transfer equation is often not solved by simulating every wavelength of light, but instead by computing tristimulus transport, for instance using sRGB primaries as a basis. This choice is convenient, because input texture data is usually stored in RGB colour spaces. However, there are problems with this approach which are often overlooked or ignored. By comparing to spectral reference renderings, we show how rendering in tristimulus colour spaces introduces colour shifts in indirect light, violation of energy conservation, and unexpected behaviour in participating media. Furthermore, we introduce a fast method to compute spectra from almost any given XYZ input colour. It creates spectra that match the input colour precisely. Additionally, like in natural reflectance spectra, their energy is smoothly distributed over wide wavelength bands. This method is both useful to upsample RGB input data when spectral transport is used and as an intermediate step for corrected tristimulus‐based transport. Finally, we show how energy conservation can be enforced in RGB by mapping colours to valid reflectances.     

SOA-enabled compliance management: instrumenting, assessing, and analyzing service-based business processes

Facilitating compliance management, that is, assisting a company’s management in conforming to laws, regulations, standards, contracts, and policies, is a hot but non-trivial task. The service-oriented architecture (SOA) has evolved traditional, manual business practices into modern, service-based IT practices that ease part of the problem: the systematic definition and execution of business processes. This, in turn, facilitates the online monitoring of system behaviors and the enforcement of allowed behaviors—all ingredients that can be used to assist compliance management on the fly during process execution. In this paper, instead of focusing on monitoring and runtime enforcement of rules or constraints, we strive for an alternative approach to compliance management in SOAs that aims at assessing and improving compliance. We propose two ingredients: (i) a model and tool to design compliant service-based processes and to instrument them in order to generate evidence of how they are executed and (ii) a reporting and analysis suite to create awareness of a company’s compliance state and to enable understanding why and where compliance violations have occurred. Together, these ingredients result in an approach that is close to how the real stakeholders—compliance experts and auditors—actually assess the state of compliance in practice and that is less intrusive than enforcing compliance.