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Jacobsen, M.

Publications and source records attributed to Jacobsen, M..

3 recordsLinked to original sources

Quantitative Comparison of 3D-1D Vascular Coupling Models: Lateral Average versus Sphere of Influence Methods

Computational models coupling one-dimensional vascular networks with three-dimensional tissue domains are widely used for predicting blood flow distribution in tumor perfusion, drug delivery, and therapeutic planning. Two prominent coupling paradigms have emerged: the Lateral Average Model (LAM) which implements distributed transmural exchange via a vessel wall conductivity parameter{gamma} (m Pa-1 s-1), and the Sphere of Influence (SOI) model, which employs localized terminal coupling via a source sphere radius{varepsilon} (m). Despite their broad application, systematic quantitative comparisons of their parametric behavior and predictive equivalence remain lacking. We compare LAM and SOI in 3D-1D simulations on a benchmark vascular network and a porcine liver study with a hepatic arterial network reconstructed from CT arteriography. Across a benchmark vascular network under three sink configurations, the LAM net flow rate rose smoothly with{gamma} and saturated at a plateau, while the SOI net flow rate increased with{varepsilon} without saturating; as a result, global-flow equivalence between the two formulations exists only for particular boundary geometries, and not at all within the tested parameter range for one of the three configurations examined. Despite this partial agreement in total flow, the two models diverged substantially in regional perfusion: in a porcine hepatic arterial network reconstructed from CT arteriography, SOI predicted stable perfusion fractions to two regions of interest across its full tested parameter range, whereas LAM predictions for the same regions varied several-fold with vessel wall permeability and, at low permeability, could invert which region received more flow. These results indicate that the choice of coupling model has limited consequence for predicted total organ flow but substantial consequence for predicted local drug delivery, and we provide guidance for selecting between the two formulations depending on the clinical or research question being asked. Author SummaryWhen doctors plan treatments for liver cancer, they often rely on computer simulations to predict how blood flows through the liver and how well a drug will reach the tumor. These simulations depend on mathematical models that describe how blood moves from vessels into surrounding tissue. Two commonly used approaches exist for building these models, but researchers have generally chosen between them based on habit or convenience rather than on a principled understanding of how their predictions differ. In this work, we directly compared these two approaches, one that spreads blood exchange continuously along the vessel wall, and one that delivers blood from the vessel tips into a surrounding spherical zone, using both a simple test network and a realistic pig liver reconstructed from medical imaging. We found that the two approaches can agree on the total amount of blood reaching the liver, but disagree substantially on where that blood goes within the tissue. This distinction matters enormously for treatment planning: a model that predicts the right total blood flow but delivers it to the wrong region of the liver could lead to an inaccurate forecast of drug concentration at the tumor site. Our results provide practical guidance for researchers on which approach to use depending on what information is available and what question is being asked.

biophysics↗

Identifying Mangrove-Coral Habitats in the Florida Keys

Coral reefs are degrading due to many synergistic stressors. Recently there have been a number of global reports of corals occupying mangrove habitats that provide a supportive environment or refugium for corals, sheltering them by reducing stressors such as oxidative light stress and low pH. This study used satellite imagery and manual ground-truthing surveys to search for mangrove-coral habitats in the Florida Keys and then collected basic environmental parameters (temperature, salinity, dissolved oxygen, pHNBS, turbidity) at identified sites using a multi-parameter water quality sonde. Two kinds of mangrove-coral habitats were found in both the Upper and Lower Florida Keys: (1) prop-root corals, where coral colonies were growing directly on (and around) mangrove prop roots, and (2) channel corals, where coral colonies were growing in mangrove channels under the shade of the mangrove canopy, at deeper depths and not in as close proximity to the mangroves. Coral species found growing on and directly adjacent to prop roots included Porites porites (multiple morphs), Siderastrea radians and Favia fragum. Channel coral habitats predominantly hosted S. radians and a few S. siderea, although single colonies of Solenastrea bournoni and Stephanocoenia intersepta were observed. Circumstantial evidence suggests additional coral communities existed on mangrove shorelines of oceanside and backcountry islands until destroyed, likely by Hurricane Irma. These mangrove-coral habitats may be climate refugia for corals and could be included in ecosystem management plans and considered for their applications in coral restoration, for example, as a source of adapted genetic resources, places to support growth and acclimation of coral outplants, or natural laboratories to test survival of different genotypes.

ecology↗

Conformational dynamics of the HIV Vif protein complex

HIV-1 viral infectivity factor (Vif) is an intrinsically disordered protein responsible for the ubiquitination of the APOBEC3 antiviral proteins. Vif folds when it binds the Cullin-RING E3 ligase CRL5 and the transcription cofactor CBF-{beta}. A five-protein complex containing the substrate receptor (Vif, CBF-{beta}, Elongin-B, Elongin-C) and Cullin5 (CUL5) has a published crystal structure, but dynamics of this VCBC-CUL5 complex have not been characterized. Here, we use Molecular Dynamics (MD) simulations and NMR to characterize the dynamics of the VCBC complex with and without CUL5 and APOBEC3 bound. Our simulations show that the VCBC complex undergoes global dynamics involving twisting and clamshell opening of the complex, while VCBC-CUL5 maintains a more static conformation, similar to the crystal structure. This observation from MD is supported by methyl-transverse relaxation optimized spectroscopy (methyl-TROSY) NMR data, which indicates that the entire VCBC complex without CUL5 is dynamic on the s-ms timescale. Vif binds APOBEC3 to recruit it to the complex, and methyl-TROSY NMR shows that the VCBC complex is more conformationally restricted when bound to APOBEC3F, consistent with our MD simulations. Vif contains a flexible linker region located at the hinge of the VCBC complex, which changes conformation in conjuction with the global dynamics of the complex. Like other ubiquitin substrate receptors, VCBC can exist alone or in complex with CUL5 in cells. Accordingly, the VCBC complex could be a good target for therapeutics that would inhibit full assembly of the ubiquitination complex by stabilizing an alternate VCBC conformation.

biophysics↗