Outflow boundary conditions for 3D simulations of non-periodic blood flow and pressure fields in deformable arteries

The simulation of blood flow and pressure in arteries requires outflow boundary conditions that incorporate models of downstream domains. We previously described a coupled multidomain method to couple analytical models of the downstream domains with 3D numerical models of the upstream vasculature. This prior work either included pure resistance boundary conditions or impedance boundary conditions based on assumed periodicity of the solution. However, flow and pressure in arteries are not necessarily periodic in time due to heart rate variability, respiration, complex transitional flow or acute physiological changes. We present herein an approach for prescribing lumped parameter outflow boundary conditions that accommodate transient phenomena. We have applied this method to compute haemodynamic quantities in different physiologically relevant cardiovascular models, including patient-specific examples, to study non-periodic flow phenomena often observed in normal subjects and in patients with acquired or congenital cardiovascular disease. The relevance of using boundary conditions that accommodate transient phenomena compared with boundary conditions that assume periodicity of the solution is discussed

Pauli blocking and medium effects in nucleon knockout reactions

We study medium modifications of the nucleon-nucleon (NN) cross sections and their influence on the nucleon knockout reactions. Using the eikonal approximation, we compare the results obtained with free NN cross sections with those obtained with a purely geometrical treatment of Pauli-blocking and with NN obtained with more elaborated Dirac-Bruecker methods. The medium effects are parametrized in terms of the baryon density. We focus on symmetric nuclear matter, although the geometrical Pauli-blocking allows for the treatment of asymmetric nuclear matter. It is shown that medium effects can change the nucleon knockout cross sections and momentum distributions up to 10% in the energy range E=50-300 MeV/nucleon. The effect is more evident in reactions involving halo nuclei.Comment: 10 pages, 9 figures, accepted for publication in Physics Review

A reduced-order modeling for efficient design study of artificial valve in enlarged ventricular outflow tracts

A computational approach is proposed for efficient design study of a reducer stent to be percutaneously implanted in enlarged right ventricular outflow tracts (RVOT). The need for such a device is driven by the absence of bovine or artificial valves which could be implanted in these RVOT to replace the absent or incompetent native valve, as is often the case over time after Tetralogy of Fallot repair. Hemodynamics are simulated in the stented RVOT via a reduce order model based on proper orthogonal decomposition (POD), while the artificial valve is modeled as a thin resistive surface. The reduced order model is obtained from the numerical solution on a reference device configuration, then varying the geometrical parameters (diameter) for design purposes. To validate the approach, forces exerted on the valve and on the reducer are monitored, varying with geometrical parameters, and compared with the results of full CFD simulations. Such an approach could also be useful for uncertainty quantification

Efficient blood flow simulations for the design of stented valve reducer in enlarged ventricular outflow tracts

Tetralogy of Fallot is a congenital heart disease characterized over time, after the initial repair, by the absence of a functioning pulmonary valve, which causes regurgitation, and by progressive enlargement of the right ventricle and pulmonary arteries. Due to this pathological anatomy, available transcatheter valves are usually too small to be deployed in the enlarged right ventricular outflow tracts (RVOT). To avoid surgical valve replacement, an alternative consists in implanting a reducer prior to or in combination with a transcatheter valve. We describe a computational model to study the effect of a stented valve RVOT reducer on the hemodynamics in enlarged ventricular outflow tracts. To this aim, blood flow in the right ventricular outflow tract is modeled via the incompressible Navier--Stokes equations coupled to a simplified valve model, numerically solved with a standard finite element method and with a reduced order model based on Proper Orthogonal Decomposition (POD). Numerical simulations are based on a patient geometry obtained from medical imaging and boundary conditions tuned according to measurements of inlet flow rates and pressures. Different geometrical models of the reducer are built, varying its length and/or diameter, and compared with the initial device-free state. Simulations thus investigate multiple device configurations and describe the effect of geometry on hemodynamics. Forces exerted on the valve and on the reducer are monitored, varying with geometrical parameters. Results support the thesis that the reducer does not introduce significant pressure gradients, as was found in animal experiments. Finally, we demonstrate how computational complexity can be reduced with POD

MobiDB-lite 3.0: fast consensus annotation of intrinsic disorder flavors in proteins

Abstract Motivation The earlier version of MobiDB-lite is currently used in large-scale proteome annotation platforms to detect intrinsic disorder. However, new theoretical models allow for the classification of intrinsically disordered regions into subtypes from sequence features associated with specific polymeric properties or compositional bias. Results MobiDB-lite 3.0 maintains its previous speed and performance but also provides a finer classification of disorder by identifying regions with characteristics of polyolyampholytes, positive or negative polyelectrolytes, low-complexity regions or enriched in cysteine, proline or glycine or polar residues. Subregions are abundantly detected in IDRs of the human proteome. The new version of MobiDB-lite represents a new step for the proteome level analysis of protein disorder. Availability and implementation Both the MobiDB-lite 3.0 source code and a docker container are available from the GitHub repository: https://github.com/BioComputingUP/MobiDB-lit

Computational Simulations for Aortic Coarctation: Representative Results From a Sampling of Patients

Treatments for coarctation of the aorta (CoA) can alleviate blood pressure (BP) gradients(D), but long-term morbidity still exists that can be explained by altered indices of hemodynamics and biomechanics. We introduce a technique to increase our understanding of these indices for CoA under resting and nonresting conditions, quantify their contribution to morbidity, and evaluate treatment options. Patient-specific computational fluid dynamics (CFD) models were created from imaging and BP data for one normal and four CoA patients (moderate native CoA: D12 mmHg, severe native CoA: D25 mmHg and postoperative end-to-end and end-to-side patients: D0 mmHg). Simulations incorporated vessel deformation, downstream vascular resistance and compliance. Indices including cyclic strain, time-averaged wall shear stress (TAWSS), and oscillatory shear index (OSI) were quantified. Simulations replicated resting BP and blood flow data. BP during simulated exercise for the normal patient matched reported values. Greatest exercise-induced increases in systolic BP and mean and peak DBP occurred for the moderate native CoA patient (SBP: 115 to 154 mmHg; mean and peak DBP: 31 and 73 mmHg). Cyclic strain was elevated proximal to the coarctation for native CoA patients, but reduced throughout the aorta after treatment. A greater percentage of vessels was exposed to subnormal TAWSS or elevated OSI for CoA patients. Local patterns of these indices reported to correlate with atherosclerosis in normal patients were accentuated by CoA. These results apply CFD to a range of CoA patients for the first time and provide the foundation for future progress in this area

Computational simulations demonstrate altered wall shear stress in aortic coarctation patients previously treated by resection with end-to-end anastomosis

Background.  Atherosclerotic plaque in the descending thoracic aorta (dAo) is related to altered wall shear stress (WSS) for normal patients. Resection with end-to-end anastomosis (RWEA) is the gold standard for coarctation of the aorta (CoA) repair, but may lead to altered WSS indices that contribute to morbidity. Methods.  Computational fluid dynamics (CFD) models were created from imaging and blood pressure data for control subjects and age- and gender-matched CoA patients treated by RWEA (four males, two females, 15 ± 8 years). CFD analysis incorporated downstream vascular resistance and compliance to generate blood flow velocity, time-averaged WSS (TAWSS), and oscillatory shear index (OSI) results. These indices were quantified longitudinally and circumferentially in the dAo, and several visualization methods were used to highlight regions of potential hemodynamic susceptibility. Results.  The total dAo area exposed to subnormal TAWSS and OSI was similar between groups, but several statistically significant local differences were revealed. Control subjects experienced left-handed rotating patterns of TAWSS and OSI down the dAo. TAWSS was elevated in CoA patients near the site of residual narrowings and OSI was elevated distally, particularly along the left dAo wall. Differences in WSS indices between groups were negligible more than 5 dAo diameters distal to the aortic arch. Conclusions.  Localized differences in WSS indices within the dAo of CoA patients treated by RWEA suggest that plaque may form in unique locations influenced by the surgical repair. These regions can be visualized in familiar and intuitive ways allowing clinicians to track their contribution to morbidity in longitudinal studies

CAID prediction portal: A comprehensive service for predicting intrinsic disorder and binding regions in proteins

Intrinsic disorder (ID) in proteins is well-established in structural biology, with increasing evidence for its involvement in essential biological processes. As measuring dynamic ID behavior experimentally on a large scale remains difficult, scores of published ID predictors have tried to fill this gap. Unfortunately, their heterogeneity makes it difficult to compare performance, confounding biologists wanting to make an informed choice. To address this issue, the Critical Assessment of protein Intrinsic Disorder (CAID) benchmarks predictors for ID and binding regions as a community blind-test in a standardized computing environment. Here we present the CAID Prediction Portal, a web server executing all CAID methods on user-defined sequences. The server generates standardized output and facilitates comparison between methods, producing a consensus prediction highlighting high-confidence ID regions. The website contains extensive documentation explaining the meaning of different CAID statistics and providing a brief description of all methods. Predictor output is visualized in an interactive feature viewer and made available for download in a single table, with the option to recover previous sessions via a private dashboard. The CAID Prediction Portal is a valuable resource for researchers interested in studying ID in proteins. The server is available at the URL: https://caid.idpcentral.org

On Coupling a Lumped Parameter Heart Model and a Three-Dimensional Finite Element Aorta Model

Aortic flow and pressure result from the interactions between the heart and arterial system. In this work, we considered these interactions by utilizing a lumped parameter heart model as an inflow boundary condition for three-dimensional finite element simulations of aortic blood flow and vessel wall dynamics. The ventricular pressure–volume behavior of the lumped parameter heart model is approximated using a time varying elastance function scaled from a normalized elastance function. When the aortic valve is open, the coupled multidomain method is used to strongly couple the lumped parameter heart model and three-dimensional arterial models and compute ventricular volume, ventricular pressure, aortic flow, and aortic pressure. The shape of the velocity profiles of the inlet boundary and the outlet boundaries that experience retrograde flow are constrained to achieve a robust algorithm. When the aortic valve is closed, the inflow boundary condition is switched to a zero velocity Dirichlet condition. With this method, we obtain physiologically realistic aortic flow and pressure waveforms. We demonstrate this method in a patient-specific model of a normal human thoracic aorta under rest and exercise conditions and an aortic coarctation model under pre- and post-interventions

The repetitive structure of DNA clamps: An overlooked protein tandem repeat

Structured tandem repeats proteins (STRPs) are a specific kind of tandem repeat proteins characterized by a modular and repetitive three-dimensional structure arrangement. The majority of STRPs adopt solenoid structures, but with the increasing availability of experimental structures and high-quality predicted structural models, more STRP folds can be characterized. Here, we describe “Box repeats”, an overlooked STRP fold present in the DNA sliding clamp processivity factors, which has eluded classification although structural data has been available since the late 1990s. Each Box repeat is a β⍺βββ module of about 60 residues, which forms a class V “beads-on-a-string” type STRP. The number of repeats present in processivity factors is organism dependent. Monomers of PCNA proteins in both Archaea and Eukarya have 4 repeats, while the monomers of bacterial beta-sliding clamps have 6 repeats. This new repeat fold has been added to the RepeatsDB database, which now provides structural annotation for 66 Box repeat proteins belonging to different organisms, including viruses