Multiscale Modeling of Biological Flow using Lattice Boltzmann Method

In this dissertation, we have developed a fluid-structure interaction code specifically designed to simulate soft microparticle deformation in biological flow. We have used this tool for two different applications. First, we study red blood cell deformation under shear flow to evaluate stress distribution on membrane and subsequently pore formation on RBC membrane. Second, we utilized this code to show a proof of concept for an idea where we can separate soft particles based on their biophysical properties. In the following, these applications are discussed in more details.Under high shear rates, pores form on RBC membrane through which hemoglobin leaks out and increases free hemoglobin content of plasma leading to hemolysis. We hypothesize that local flow dynamics such as flow rate and shear stress determines blood cell damage. In this dissertation, a novel model is presented to study red blood cell (RBC) hemolysis at cellular level. The goal of the proposed work is to establish multiscale computational techniques to predict the blood cell dynamics and damage in complex flow conditions, i.e., blood-wetting biomedical devices. The cell membrane damage model will be coupled with local fluid flow to study cell deformation and rupture and a generalized cellular level blood cell damage model will be developed based on these simulations. By coupling Lattice Boltzmann and spring connected network models through immersed boundary method, we estimate hemolysis of a single red blood cell under various shear rates. First, we use adaptive meshing to find local strain distribution and critical sites on RBC membrane, then we apply underlying molecular dynamic simulations to evaluate damage. Our approach is comprised of three sub-models: defining criteria of pore formation, calculating pore size, and measuring Hb diffusive flux out of pores. Our damage model uses information of different scales to predict cellular level hemolysis. Results are compared with experimental studies and other models in literature. The developed cellular damage model can be used as a predictive tool for hydrodynamic and hematologic design optimization of blood-wetting medical devices.Isolating cells of interest from a heterogeneous mixture has been of critical importance in biological studies and clinical applications. In this dissertation, we have proposed to use ciliary system in microfluidic devices to isolate target subpopulation of soft particles based on their biophysical properties. In this model, the bottom of microchannel is covered with an equally spaced cilia array which can be magnetically actuated. A series of simulations are performed to study cilia-particle interaction and isolation dynamic. It is shown that these elastic hair-like filaments can influence particle’s trajectories differently depending on their biophysical properties. This modeling study also uses immersed boundary (IB) method coupled with lattice Boltzmann method. Soft particles are simulated by connected network of nonlinear springs. Moreover, cilia is modeled by point-particle scheme. It is demonstrated that active ciliary system is able to continuously and non-destructively sort cells based on their size, shape and stiffness. Ultimately, a design map for fabrication of a programmable microfluidic device capable of isolating various subpopulation of cells is developed. This biocompatible, label-free design can separate cells/soft microparticles with high throughput which can greatly complement existing separation technologies

Oleic Acid Protects Caenorhabditis Mothers From Mating-Induced Death and the Cost of Reproduction

Reproduction comes at a cost, including accelerated death. Previous studies of the interconnections between reproduction, lifespan, and fat metabolism in C. elegans were predominantly performed in low-reproduction conditions. To understand how increased reproduction affects lifespan and fat metabolism, we examined mated worms; we find that a Δ9 desaturase, FAT-7, is significantly up-regulated. Dietary supplementation of oleic acid (OA), the immediate downstream product of FAT-7 activity, restores fat storage and completely rescues mating-induced death, while other fatty acids cannot. OA-mediated lifespan restoration is also observed in C. elegans mutants suffering increased death from short-term mating, and in mated C. remanei females, indicating a conserved role of oleic acid in post-mating lifespan regulation. Our results suggest that increased reproduction can be uncoupled from the costs of reproduction from somatic longevity regulation if provided with the limiting lipid, oleic acid

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Characterization of Nanoparticle Dispersion in Red Blood Cell Suspension by the Lattice Boltzmann-Immersed Boundary Method

Nanodrug-carrier delivery in the blood stream is strongly influenced by nanoparticle (NP) dispersion. This paper presents a numerical study on NP transport and dispersion in red blood cell (RBC) suspensions under shear and channel flow conditions, utilizing an immersed boundary fluid-structure interaction model with a lattice Boltzmann fluid solver, an elastic cell membrane model and a particle motion model driven by both hydrodynamic loading and Brownian dynamics. The model can capture the multiphase features of the blood flow. Simulations were performed to obtain an empirical formula to predict NP dispersion rate for a range of shear rates and cell concentrations. NP dispersion rate predictions from the formula were then compared to observations from previous experimental and numerical studies. The proposed formula is shown to accurately predict the NP dispersion rate. The simulation results also confirm previous findings that the NP dispersion rate is strongly influenced by local disturbances in the flow due to RBC motion and deformation. The proposed formula provides an efficient method for estimating the NP dispersion rate in modeling NP transport in large-scale vascular networks without explicit RBC and NP models

PINK-1 mitophagy is specifically required for <i>daf-2</i> reproductive span.

(A) mtRosella is silenced in the germline. Image of the dissected germline of the WMB1119 strain with Ppie-1TOMM-20::Rosella insert. Image was captured on the Nikon eclipse Ti at 60x magnification. The mCherry and FITC channels are superimposed Z-stacks taken at 0.7μm steps. (B) Mating capability of all genotypes used in this study when young hermaphrodites are mated with fog-2 males. (C) Late-mating capability in pink-1 vs. N2. Day 7 adults are mated with young males. (D) Lifespan of pink-1(tm1779) (n = 62) is unchanged compared to N2 (n = 69). (PDF)</p

Representative Z-stack of mitochondria in the -1 oocyte of Day 7 adult <i>daf-2(e1370)</i>, 60x.

(AVI)</p

Representative Z-stack of mitochondria in the -1 oocyte of Day 7 adult <i>daf-2(e1370)</i>, 100x.

(AVI)</p