StarPhase: Comprehensive Phase-Aware Pharmacogenomic Diplotyper for Long-Read Sequencing Data.

Pharmacogenomics is central to precision medicine, informing medication safety and efficacy. Pharmacogenomic diplotyping of complex genes requires full-length DNA sequences and detection of structural rearrangements. We introduce StarPhase, a tool that leverages PacBio HiFi sequence data to diplotype 21 CPIC Level A pharmacogenes and provides detailed haplotypes and supporting visualizations for , , and .

Simulation of perovskite thin layer crystallization with varying evaporation rates.

Perovskite solar cells (PSC) are promising potential competitors to established photovoltaic technologies due to their superior efficiency and low-cost solution processability. However, the limited understanding of the crystallization behaviour hinders the technological transition from lab-scale cells to modules. In this work, advanced phase field (PF) simulations of solution-based film formation are used for the first time to obtain mechanistic and morphological information that is experimentally challenging to access.

Precision of Radiation Chemistry Networks: Playing Jenga with Kinetic Models for Liquid-Phase Electron Microscopy.

Liquid-phase transmission electron microscopy (LP-TEM) is a powerful tool to gain unique insights into dynamics at the nanoscale. The electron probe, however, can induce significant beam effects that often alter observed phenomena such as radiolysis of the aqueous phase. The magnitude of beam-induced radiolysis can be assessed by means of radiation chemistry simulations potentially enabling quantitative application of LP-TEM.

The interplay of shape and catalyst distribution in the yield of compressible flow microreactors.

We develop a semi-analytical model for transport in structured catalytic microreactors, where both reactant and product are compressible fluids. Using lubrication and Fick-Jacobs approximations, we reduce the three-dimensional governing equations to an effective one-dimensional set of equations. Our model captures the effect of compressibility, corrugations in the shape of the reactor, and an inhomogeneous catalytic coating of the reactor walls.

Lattice Boltzmann approach for acoustic manipulation.

We employ a lattice Boltzmann method to compute the acoustic radiation force produced by standing waves on a compressible object for the density matched case. Instead of simulating the fluid mechanics equations directly, the proposed method uses a lattice Boltzmann model that reproduces the wave equation, together with a kernel interpolation scheme, to compute the first-order perturbations of the pressure and velocity fields on the object's surface and, from them, the acoustic radiation force. The procedure reproduces with excellent accuracy the theoretical expressions by Gor'kov and Wei for the sphere as the 3D case and an infinitely long cylinder as the 2D case, respectively, even with a modest number of lattice Boltzmann cells.

Enhancement of bubble transport in porous electrodes and catalysts.

We investigate the formation and transport of gas bubbles across a model porous electrode/catalyst using lattice Boltzmann simulations. This approach enables us to systematically examine the influence of a wide range of morphologies, flow velocities, and reaction rates on the efficiency of gas production. By exploring these parameters, we identify critical parameter combinations that significantly contribute to an enhanced yield of gas output.

Closing the gap: Solving complex medically relevant genes at scale.

Comprehending the mechanism behind human diseases with an established heritable component represents the forefront of personalized medicine. Nevertheless, numerous medically important genes are inaccurately represented in short-read sequencing data analysis due to their complexity and repetitiveness or the so-called 'dark regions' of the human genome. The advent of PacBio as a long-read platform has provided new insights, yet HiFi whole-genome sequencing (WGS) cost remains frequently prohibitive.

Local electroneutrality breakdown for electrolytes within varying-section nanopores.

We determine the local charge dynamics of a [Formula: see text] electrolyte embedded in a varying-section channel. By means of an expansion based on the length scale separation between the axial and transverse direction of the channel, we derive closed formulas for the local excess charge for both, dielectric and conducting walls, in 2D (planar geometry) as well as in 3D (cylindrical geometry). Our results show that, even at equilibrium, the local charge electroneutrality is broken whenever the section of the channel is not homogeneous for both dielectric and conducting walls as well as for 2D and 3D channels.

Patterns in bottlenecks for implementation of health promotion interventions: a cross-sectional observational study on intervention-context interactions in the Netherlands.

Background: From a complex systems perspective, implementation should be understood as the introduction of an intervention in a context with which it needs to interact in order to achieve its function in terms of improved health. The presence of intervention-context interactions could mean that during implementation particular patterns of crucial interaction points might arise. We examined the presence of - and regularities in - such 'bottlenecks for implementation', as this could create opportunities to predict and intervene in potential implementation problems.

Turning catalytically active pores into active pumps.

We develop a semi-analytical model of self-diffusioosmotic transport in active pores, which includes advective transport and the inverse chemical reaction that consumes solute. In previous work [Antunes et al., Phys.

Cell-free layer development and spatial organization of healthy and rigid red blood cells in a microfluidic bifurcation.

Bifurcations and branches in the microcirculation dramatically affect blood flow as they determine the spatiotemporal organization of red blood cells (RBCs). Such changes in vessel geometries can further influence the formation of a cell-free layer (CFL) close to the vessel walls. Biophysical cell properties, such as their deformability, which is impaired in various diseases, are often thought to impact blood flow and affect the distribution of flowing RBCs.

Closed Formula for Transport across Constrictions.

In the last decade, the Fick-Jacobs approximation has been exploited to capture transport across constrictions. Here, we review the derivation of the Fick-Jacobs equation with particular emphasis on its linear response regime. We show that, for fore-aft symmetric channels, the flux of noninteracting systems is fully captured by its linear response regime.

Diffusion of gold nanoparticles in porous silica monoliths determined by dynamic light scattering.

Hypothesis: The applicability of the dynamic light scattering method for the determination of particle diffusivity under confinement without applying refractive index matching was not adequately explored so far. The confinement effect on particle diffusion in a porous material which is relevant for particle chromatography has also not yet been fully characterized.

Experiments: Dynamic light scattering experiments were performed for unimodal dispersions of 11-mercaptoundecanoic acid-capped gold nanoparticles.

Comprehensive SMN1 and SMN2 profiling for spinal muscular atrophy analysis using long-read PacBio HiFi sequencing.

Spinal muscular atrophy, a leading cause of early infant death, is caused by bi-allelic mutations of SMN1. Sequence analysis of SMN1 is challenging due to high sequence similarity with its paralog SMN2. Both genes have variable copy numbers across populations.

An efficient genotyper and star-allele caller for pharmacogenomics.

High-throughput sequencing provides sufficient means for determining genotypes of clinically important pharmacogenes that can be used to tailor medical decisions to individual patients. However, pharmacogene genotyping, also known as star-allele calling, is a challenging problem that requires accurate copy number calling, structural variation identification, variant calling, and phasing within each pharmacogene copy present in the sample. Here we introduce Aldy 4, a fast and efficient tool for genotyping pharmacogenes that uses combinatorial optimization for accurate star-allele calling across different sequencing technologies.

Technological Pathways to Produce Compressed and Highly Pure Hydrogen from Solar Power.

Hydrogen (H ) produced from renewables will have a growing impact on the global energy dynamics towards sustainable and carbon-neutral standards. The share of green H is still too low to meet the net-zero target, while the demand for high-quality hydrogen continues to rise. These factors amplify the need for economically viable H generation technologies.

Rolling microswarms along acoustic virtual walls.

Rolling is a ubiquitous transport mode utilized by living organisms and engineered systems. However, rolling at the microscale has been constrained by the requirement of a physical boundary to break the spatial homogeneity of surrounding mediums, which limits its prospects for navigation to locations with no boundaries. Here, in the absence of real boundaries, we show that microswarms can execute rolling along virtual walls in liquids, impelled by a combination of magnetic and acoustic fields.

Nucleation as a rate-determining step in catalytic gas generation reactions from liquid phase systems.

The observable reaction rate of heterogeneously catalyzed reactions is known to be limited either by the intrinsic kinetics of the catalytic transformation or by the rate of pore and/or film diffusion. Here, we show that in gas generation reactions from liquid reactants, the nucleation of gas bubbles in the catalyst pore structure represents an additional important rate-limiting step. This is highlighted for the example of catalytic hydrogen release from the liquid organic hydrogen carrier compound perhydro-dibenzyltoluene.

Pumping and Mixing in Active Pores.

We show both numerically and analytically that a chemically patterned active pore can act as a micro- or nanopump for fluids, even if it is fore-aft symmetric. This is possible due to a spontaneous symmetry breaking which occurs when advection rather than diffusion is the dominant mechanism of solute transport. We further demonstrate that, for pumping and tuning the flow rate, a combination of geometrical and chemical inhomogeneities is required.

Formation of Crystalline Bulk Heterojunctions in Organic Solar Cells: Insights from Phase-Field Simulations.

The performance of organic solar cells strongly depends on the bulk-heterojunction (BHJ) morphology of the photoactive layer. This BHJ forms during the drying of the wet-deposited solution, because of physical processes such as crystallization and/or liquid-liquid phase separation (LLPS). However, the process-structure relationship remains insufficiently understood.

Long-read HiFi sequencing of NUDT15: Phased full-gene haplotyping and pharmacogenomic allele discovery.

To determine the phase of NUDT15 sequence variants for more comprehensive star (*) allele diplotyping, we developed a novel long-read single-molecule real-time HiFi amplicon sequencing method. A 10.5 kb NUDT15 amplicon assay was validated using reference material positive controls and additional samples for specimen type and blinded accuracy assessment.

Accuracy and performance of the lattice Boltzmann method with 64-bit, 32-bit, and customized 16-bit number formats.

Fluid dynamics simulations with the lattice Boltzmann method (LBM) are very memory intensive. Alongside reduction in memory footprint, significant performance benefits can be achieved by using FP32 (single) precision compared to FP64 (double) precision, especially on GPUs. Here we evaluate the possibility to use even FP16 and posit16 (half) precision for storing fluid populations, while still carrying arithmetic operations in FP32.

Participatory research in health promotion: a critical review and illustration of rationales.

In health promotion research, enthusiasm for patient and public involvement (PPI) is growing. However, a lack of conceptual clarity leads to ambiguities in participatory processes and purposes, and hampers efforts to achieve and evaluate PPI in research. This study provides an overview of its underlying reasons-or rationales-so as to better understand, guide and interpret PPI in research practice.