Generic Geometric Programming in the Computational Geometry Algorithms Library

This paper describes a number of design issues and programming paradigms that affect the development of C gal , the computational geometry algorithms library. Genericity of the library is achieved by concepts such as templates, iterators, and traits classes. This allows the application programmer to plug in own types of containers and point types, for example. The paper gives an explanation of these concepts and examples of how they are used.     

Whey protein aggregates and their interaction with exo-polysaccharides

Summary We made a systematic investigation of the interaction of an exo-polysaccharide (EPS) with whey proteins. The EPS was produced by a lactic acid bacterium Lactococcus lactis subsp. cremoris strain NIZO B40. The interaction of the EPS with milk components is of relevance to the consistency of fermented milk products. EPS and whey protein isolates (WPI) can be mixed in all proportions. Even at an EPS concentration of 10 g.L⁻¹ no instability is visible. In yoghurt milk the whey proteins are usually denatured. We prepared aggregated whey protein colloid particles (AWC particles) which had an average radius of 27 ± 3 nm, as derived from the radius of gyration. The interaction of AWC particles and EPS was studied at a neutral pH and an ionic strength of 0.1 m. At low EPS concentrations the mixture was stable. At higher concentrations the mixtures showed phase separation owing to depletion interactions. In the one-phase region the strength of the segregative interaction can be determined from turbidity, light scattering and neutron scattering measurements. Then, by applying statistical mechanical methods, the position of the phase boundary could be predicted. The viscosity of the mixtures was increased owing to the segregative interactions in the EPS/AWC mixtures. Within the two-phase region the mixtures showed so-called spinodal decomposition, during which different microstructures were formed. Understanding the formation of such structures is of interest for the development of new food structures.     

A maximal monotone impact law for the 3-ball Newton’s cradle

The 3-ball Newton’s cradle is used as a stepping stone to divulge the structure of impact laws. A continuous conewise linear impact law that maps the preimpact contact velocities to the postimpact contact velocities is proposed for the 3-ball Newton’s cradle. The proposed impact law is kinematically, kinetically, and energetically consistent. It reproduces the outcomes of experimental observation. Moreover, it is in accordance with the outcome of the collision of three identical linear-elastic thin rods for which the impact process is governed by the one-dimensional wave equation. The proposed impact law is shown to be nonexpansive. Therefore, the relationship between the mean contact velocity and its dual, the impulsive force, is maximal monotone. A counterexample to maximal cyclical monotonicity of this relationship allows us to conclude that no dissipation function exists for the proposed impact law.     

The role of inter-regional mobility in forecasting SARS-CoV-2 transmission

In this paper, we present a method to forecast the spread of SARS-CoV-2 across regions with a focus on the role of mobility. Mobility has previously been shown to play a significant role in the spread of the virus, particularly between regions. Here, we investigate under which epidemiological circumstances incorporating mobility into transmission models yields improvements in the accuracy of forecasting, where we take the situation in The Netherlands during and after the first wave of transmission in 2020 as a case study. We assess the quality of forecasting on the detailed level of municipalities, instead of on a nationwide level. To model transmissions, we use a simple mobility-enhanced SEIR compartmental model with subpopulations corresponding to the Dutch municipalities. We use commuter information to quantify mobility, and develop a method based on maximum likelihood estimation to determine the other relevant parameters. We show that taking inter-regional mobility into account generally leads to an improvement in forecast quality. However, at times when policies are in place that aim to reduce contacts or travel, this improvement is very small. By contrast, the improvement becomes larger when municipalities have a relatively large amount of incoming mobility compared with the number of inhabitants.     

Drug Repurposing for Cystic Fibrosis: Identification of Drugs That Induce CFTR-Independent Fluid Secretion in Nasal Organoids

Individuals with cystic fibrosis (CF) suffer from severe respiratory disease due to a genetic defect in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which impairs airway epithelial ion and fluid secretion. New CFTR modulators that restore mutant CFTR function have been recently approved for a large group of people with CF (pwCF), but ~19% of pwCF cannot benefit from CFTR modulators Restoration of epithelial fluid secretion through non-CFTR pathways might be an effective treatment for all pwCF. Here, we developed a medium-throughput 384-well screening assay using nasal CF airway epithelial organoids, with the aim to repurpose FDA-approved drugs as modulators of non-CFTR-dependent epithelial fluid secretion. From a ~1400 FDA-approved drug library, we identified and validated 12 FDA-approved drugs that induced CFTR-independent fluid secretion. Among the hits were several cAMP-mediating drugs, including β2-adrenergic agonists. The hits displayed no effects on chloride conductance measured in the Ussing chamber, and fluid secretion was not affected by TMEM16A, as demonstrated by knockout (KO) experiments in primary nasal epithelial cells. Altogether, our results demonstrate the use of primary nasal airway cells for medium-scale drug screening, target validation with a highly efficient protocol for generating CRISPR-Cas9 KO cells and identification of compounds which induce fluid secretion in a CFTR- and TMEM16A-indepent manner.     

Survey on the Analysis of User Interactions and Visualization Provenance

There is fast-growing literature on provenance-related research, covering aspects such as its theoretical framework, use cases, and techniques for capturing, visualizing, and analyzing provenance data. As a result, there is an increasing need to identify and taxonomize the existing scholarship. Such an organization of the research landscape will provide a complete picture of the current state of inquiry and identify knowledge gaps or possible avenues for further investigation. In this STAR, we aim to produce a comprehensive survey of work in the data visualization and visual analytics field that focus on the analysis of user interaction and provenance data. We structure our survey around three primary questions: (1) WHY analyze provenance data, (2) WHAT provenance data to encode and how to encode it, and (3) HOW to analyze provenance data. A concluding discussion provides evidence-based guidelines and highlights concrete opportunities for future development in this emerging area. The survey and papers discussed can be explored online interactively at https://provenance-survey.caleydo.org .     

Automated correction of spin-history related motion artefacts in fMRI: simulated and phantom data

This paper concerns the problem of correcting spin-history artefacts in fMRI data. We focus on the influence of through-plane motion on the history of magnetization. A change in object position will disrupt the tissue's steady-state magnetization. The disruption will propagate to the next few acquired volumes until a new steady state is reached. In this paper we present a simulation of spin-history effects, experimental data, and an automatic two-step algorithm for detecting and correcting spin-history artefacts. The algorithm determines the steady-state distribution of all voxels in a given slice and indicates which voxels need a spin-history correction. The spin-history correction is meant to be applied before standard realignment procedures. To obtain experimental data a special phantom and an MRI compatible motion system were designed. The effect of motion on spin-history is presented for data obtained using this phantom inside a 1.5-T MRI scanner. We show that the presented algorithm is capable of detecting the occurrence of a displacement, and it determines which voxels need a spin-history correction. The results of the phantom study show good agreement with the simulations.     

A high-resolution 2-DH numerical scheme for process-based modeling of 3-D turbidite fan stratigraphy

A generic three-dimensional process-based model is presented, aimed at simulation of the construction of turbidite fan stratigraphy by low-density turbidity current events. It combines theoretical formulations on density flow and sediment transport of multiple grain sizes to simulate 2-DH turbidity current flow and sedimentation over arbitrary topography. The model is solved on a rectangular grid by means of a robust and efficient second-order finite-difference approximation. A high-resolution shock-capturing technique is employed to accurately model the speed and shape of the discontinuous flow front. In this paper, the implementation of such a high-resolution scheme is explained in detail. Efficiency and robustness of the numerical solution are tested by comparing modeled flow behavior and sedimentation to measurements from flume-tank experiments in which turbidity currents interacted with obstacles representative of a tectonically deformed basin floor. Results illustrate that the interaction of the flow with the obstacles is realistically simulated, and that the experimental deposit geometries are reasonably well reproduced. Stability of the model depends on the length of the computational time step and the properties of the adopted flux limiter function. Run time of the simulations is somewhat shorter than the real-time duration of the experiments, which is deemed acceptable considering the small computational time step which must be adopted to keep the model stable at this small scale. At the much larger scale of real-world turbidity currents a much larger computational time step can be adopted, which will speed up simulation considerably.