Dimensional Flow Research Articles

Thermophoresis and Brownian motion effects on 3D flow of Casson nanofluid consisting microorganisms over a Riga plate using PSO: A numerical study

The objective of this research work is to analyze the nature of heat and mass transfer on 3D flow of Casson nanofluid that comprise of gyrotactic microorganisms over a Riga plate with modified magnetic field, thermophoresis and Brownian motion. The three dimensional flow, energy, diffusion and microorganisms equations are solved by numerical integration scheme along with PSO “Particle Swarm Optimization”. In this overall analysis, the patterns of temperature, velocities, concentration and gyrotactic microorganisms for Casson nanofluid are depicted due to existing parameters. From this study, it has been noted that due to increase in Casson factor and Brownian motion parameter values, mass transfer rate of working fluid is depreciated. Moreover, motile gyrotactic microorganisms profiles declined with increase in values of Peclet number, Hartmann number, Brownian and bioconvection parameters.

Black Hole Supertranslations and Hydrodynamic Enstrophy.

We study the relation between approximate horizon symmetries of AdS black branes and approximately conserved currents in their dual hydrodynamic description. We argue that the existence of an approximately conserved enstrophy current unique to 2+1 dimensional fluid flow implies that AdS_{4} black branes possess a special class of approximate supertranslations (which we identify).

Probabilistic representation of helicity in viscous fluids

It is shown that the helicity of three dimensional viscous incompressible flow can be identified with the overall linking of the fluid's initial vorticity to the expectation of a stochastic mean field limit. The relevant mean field limit is obtained by following the Lagrangian paths in the stochastic Hamiltonian interacting particle system of [S. Hochgerner, Proc. R. Soc. A 474:20180178].

A hybrid nanofluid analysis near a parabolic stretched surface

Two dimensional incompressible steady viscous nano-fluid flow with the impacts of heat generation and porous medium is examined numerically. For this objective Ti6Al4v are taken as nano-particles dispersed in different base fluids such as methanol, engine oil and water. Basically in this study we will compare three different nano-fluids to assess their flow behaviour and thermal performance. The flow model is developed under certain assumptions. The two dimensional non-linear PDEs are converted into non-linear ODEs with suitable transformation. The numerical procedure is adopted to find the results by using Bvp4c technique in MATLAB. Moreover, graphs are generated for various parameters against the temperature and velocity profiles. The fluid behaviour for different parameter is examined on velocity and temperature profile. It is depicted that for high values of volume fraction and curvature parameter nano-particles leads to high velocity and temperature profile. Moreover, velocity profile decreases for permeability parameter, while temperature profile enhances for heat generation parameter. The influence of Nusselt number and skin friction also assessed. The model of entropy generation is also presented.

IMMU-01. Combining CD28 and 4-1BB costimulationin trans enhances the anti-glioma efficacy and persistence of B7-H3 CAR T cells in immune-competent brain tumor models

We and others have demonstrated that B7-H3 CAR T-cells have potent antitumor responses in xenograft models for brain tumors; however, these models do not recapitulate the immunosuppressive tumor microenvironment (TME) in patients with high-grade glioma. To evaluate the safety and efficacy of antigen-specific CAR T-cells, we adapted the immune-competent GL261 glioma model which recapitulates human disease and host immune barriers. We generated a library of B7-H3 CARs with different transmembrane (CD8, CD28), costimulatory (CD28, 4-1BB), and activation (ζ, mutζ) domains. We then compared their cytolytic activity, expansion, and anti-tumor activity. Results show that B7-H3 CARs with CD28 transmembrane and costimulatory domains have superior efficacy compared to CARs with CD8 and 4-1BB domains. Additionally, CARs with mutated ζ activation domain have better overall persistence. However, providing costimulation signals through CD28 or 4-1BB alone does not induce superior anti-glioma efficacy of B7-H3 CAR T-cells in vivo. Thus, we next investigated whether incorporating 4-1BB signaling into CD28-based CARs using in trans design enhances the therapeutic efficacy of B7-H3 CAR T-cells. We found that in repeat stimulation assays, surface expression of 4-1BBL enhanced expansion of B7H3 CAR T-cells at least 300-folds more than T-cells with CD28 or 4-1BB costimulatory domains alone. Additionally, 4-1BBL expression significantly enhanced the sequential killing capacity compared to CD28- or 41BB-based B7-H3 CAR T-cells. High dimensional flow cytometry analysis of GL261 tumors post CAR T-cell injection revealed unique immune clusters including dendritic cells and lymphoid predominant populations in mice treated with 4-1BBL expressing CARs. Thus, expression of 4-1BBL on CD28-based CARs reshaped the TME and enhanced persistence and anti-glioma efficacy of B7-H3 CAR T-cells. Studies examining transcriptional and epigenetic programs, and TME/CAR T-cell interactions are in progress. Results will define pathways that dictate CAR T-cell performance and will identify unique mechanisms for further improvements utilizing other members of TNF-superfamily.

Impacts of the properties heterogeneity on 3D magnetic dusty nanofluids flow in porous enclosures with cylinders

This paper examines the controlling of the three dimensional dusty nanofluid flow using the two circular cylinders having different thermal conditions. The cylinders are located in the middle area while the location of the right cylinder is changeable. The 3D (three dimensional) cubic flow domain is filled by a non-Darcy porous medium and a magnetic field in Z-direction is taken place. The non-homogeneous two phase model of the nanofluid is applied while the permeability and thermal conductivity of the porous medium are assumed heterogonous. The current situation is represented by two systems of the equations for the nanofluid and dusty phases. The solutions methodology is depending on the 3D SIMPLE scheme together with the finite volume method. Here, It is focused on the distance between the cylinders delta, (0.3le delta le 0.6), the Darcy number Da, ({10}^{-2}le Dale {10}^{-5}), the dusty parameter {alpha }_{d},(0.001le {alpha }_{d}le 0.1), the average nano-parameter {phi }_{av},(0.01le {phi }_{av}le 0.03). The major outcomes indicating to that the flow can be well controlled using the inner isothermal cylinders. Also, the cases of the heterogeneity in X{-}Y and X{-}Z directions give the lowest values of {Nu}_{av}. Both the flow and heat transfer rate are enhanced as delta is increased.

Design of a Thermoelectric Device for Power Generation through Waste Heat Recovery from Marine Internal Combustion Engines

Modern ships discharge large amounts of energy into the environment. More specifically, internal combustion engines (ICE) of commercial and passenger ships waste significant amounts of thermal energy at high temperature through their exhaust gases that are discharged to the atmosphere. A practical approach of recovering some amount of this energy is by using thermoelectric generator systems, which can convert thermal into electrical energy, given that there is a significant temperature difference. It is the aim of this work to propose a thermoelectric generator to recover energy from the exhaust gases of marine ICEs. The proposed thermoelectric generator uses the outside surface of the ICE manifold as the hot side of the thermoelectric module, while the cold side is maintained at a low temperature through a heat sink and induced water flow. The goal of this work is to design this thermoelectric generator and identify the configuration that produces the maximum electric power. The analysis and design are performed with the use of modeling and simulation, while commercial software is employed to study the 3-dimensional coupled fluid flow and heat transfer at a steady state. A sensitivity analysis is carried out to identify the parameters with the highest influence on power production. In addition to a full factorial sensitivity analysis, the more efficient Latin hypercube sampling is used. The analysis shows that significant energy of the exhaust gases can be converted into electric power with the use of an optimized heatsink, which creates the highest temperature difference between the two sides of the thermoelectric module.

Effects of cylinder cross-sectional geometry and blockage ratio on VIV-based mixing performance in two dimensional laminar channel flow

A novel self-sustained flow mixing methodology is numerically studied that takes advantage of the crosswise vortex induced vibrations (VIVs) of an elastically-suspended cylinder to enhance mass mixing of two coflowing miscible identical laminar streams of different concentrations within a two dimensional parallel-plate straight channel. The effects of mixer cross-sectional shape, channel blockage ratio, and reduced flow velocity on the main flow field and mixing performance characteristics are examined through extensive two dimensional CFD-based numerical simulations at low Reynolds and moderate Péclet numbers (Re=100,Pe=103). Five important canonical configurations (namely, circular, square, tilted square, tilted elliptical, and vertical elliptical) for three different blockage ratios (β=D/H=2/5, 1/4, 1/6) are considered. Numerical results indicate that the best overall mixing efficiency (over 90%) and mixing energy cost (about 8 units) are simultaneously obtained for the stationary vertical elliptical and tilted square cylinders set in the narrow channel (β=2/5), while the VIV-based mixing design does not lead to any appreciable improvements in the (already excellent) mixing performance parameters for these two specific configurations. Also, the greatest overall enhancements in the VIV-based mixing efficiencies in the order of preference are obtained for the square (up to 51%), circular (up to 39%), and tilted elliptical (up to 38%) cross sections in the lower VIV branch for the channel with highest blockage ratio (β=2/5), while the best general improvements in the mixing energy costs are achieved for the square and tilted elliptical cross sections. The overall validity of adopted computational methodology is rigorously verified against data available in the literature.

Analysis of sensitivity of thermal conductivity and variable viscosity on wall heat flux in flow of viscous fluid over a porous wedge

The author aims to discuss sensitivity of pertained parameter for a two dimensional convective wedge flow of Newtonian fluid having varying viscosity and conductivity over a semipermeable wedge surface using Response Surface Methodology (RSM). The transformed boundary layer equations forms partial differential equations which in turn are becomes a set of non-linear ordinary differential equations by use of regular perturbation method. These systems are solved numerically by the use of Matlab built in routine bvp4c respectively. The obtained results found quite comparable with those already presented in literature by other methodologies. We have made a statistical experimental design based on parametric ranges of governing parameters of the problem. We have then calculated the local wall shear stress and local wall heat flux numbers as responses for all combination of parameters in experimental design. Then we use RSM by using Central Composite Design (CCD) in order to develop a correlation between responses either Cfx or Nux and governing parameters of the problem. After developing a best fitted response surfaces for each of the response variables we have performed a detailed sensitivity analysis for each of the response surface.

DEM studies on the effect of particle breakage on the critical state behaviours of granular soils under undrained shear conditions

A number of discrete element analyses of undrained triaxial shear tests on crushable assemblies are performed using 3-dimensional particle flow code (PFC3D). The undrained shear of the samples is simulated by assigning different velocities at the boundaries to control the constant volume of the samples during the shear. Particle breakage is studied using the octahedral shear stress breakage criterion and the fragment spawning mode satisfying an Apollonian sphere packing. The microparameters of the soils are obtained by simulating the test results reported on a Nansha calcareous sand. The effects of particle breakage and drainage condition on the critical state behaviours of the sand are intensively examined. It is found that particle breakage and drainage condition do not affect the slope of the critical state p′−q line. In the ecs−(p′cs/pa)0.7 space, the critical state line translates downward and rotates clockwise when particle breakage is considered, whilst drainage condition does not affect the critical state line. The intrinsic macro–micro correlations underlying the critical state behaviours are explored by analysing the evolution of representative micromechanical indicators such as coordination number, redundancy ratio, and fabric and force anisotropies.

Diffuse large B-cell lymphoma (DLBCL) is infiltrated with activated CD8+ T-cells despite immune checkpoint signaling.

BackgroundB-cell non-Hodgkin lymphomas (NHL) are hematologic malignancies that arise in the lymph node. Despite this, the malignant cells are not cleared by the immune cells present. The failure of anti-tumor immunity may be due to immune checkpoints such as the PD-1/PDL-1 axis, which can cause T-cell exhaustion. Unfortunately, unlike Hodgkin lymphoma, checkpoint blockade in NHL has shown limited efficacy.MethodsWe performed an extensive functional analysis of malignant and non-malignant lymph nodes using high dimensional flow cytometry. We compared follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), and lymph nodes harboring reactive hyperplasia (RH).ResultsWe identified an expansion of CD8+PD1+ T-cells in the lymphomas relative to RH. Moreover, we demonstrate that these cells represent a mixture of activated and exhausted T-cells in FL. In contrast, these cells are nearly universally activated and functional in DLBCL. This is despite expression of counter-regulatory molecules such as PD-1, TIM-3, and CTLA-4, and the presence of regulatory T-cells.ConclusionThese data may explain the failure of single-agent immune checkpoint inhibitors in the treatment of DLBCL. Accordingly, functional differences of CD8+ T-cells between FL and DLBCL may inform future therapeutic targeting strategies.

Children with Multi-System Inflammatory Syndrome (MIS-C) develop functionally competent T cell memory against SARS-CoV-2 following recovery

Abstract While pediatric SARS-CoV-2 infection is largely spared from severe COVID-19, a small fraction of children develop a life-threatening condition known as MIS-C, which is associated with an aberrant peripheral blood immunophenotype; namely within adaptive immune cell populations. Little is known about how MIS-C impacts memory generation that would be imperative for future SARS-CoV-2 responses. Here, we used high dimensional flow cytometry and TCR sequencing to assess the peripheral blood T cell profile during acute MIS-C (n=17), following recovery (MIS-C-R) up to 9 months post-MIS-C (n=9), and relative to age-matched convalescent, mild pediatric COVID-19 (non-MIS-C; n=5) and uninfected controls (n=3). We also applied antigen-specific analyses to determine the magnitude and functional capacity of SARS-CoV-2-specific T cells in MIS-C-R (n=10) and non-MIS-C children (n=16). Flow cytometry showed unique T cell composition in MIS-C which resolved in recovery: lacking persistence of exhausted CD8+ T cells observed during MIS-C, and reestablishment of the naïve T cell pool. TCR sequencing showed decreased clonal diversity and distinct TCR Vβ usage in acute MIS-C compared to MIS-C-R. Results from antigen-specific analyses show that while T cell memory is similar phenotypically, MIS-C-R children have greater frequencies of SARS-CoV-2-specific CD4+ T cells than non-MIS-C up to 9 months since diagnosis. Meanwhile, SARS-CoV-2-specific CD8+ T cells in MIS-C children were more cytokine-producing, while more cytotoxic in non-MIS-C children. Together, these results reveal a restoration in global T cell phenotype in MIS-C-R children, as well as the robust production of functionally competent SARS-CoV-2 specific T cell memory. This work is supported by grants from NIH (K23 AI141686, 3U01 AI100119-10S1)

Early Life Development of Bronchial Associated Lymphoid Tissue Containing Germinal Center in the Human Lung

Abstract Early life susceptibility to respiratory pathogens is well established in infants and young children, however the specific adaptations of the infant immune system for responding to multiple respiratory challenges are not known. Here, we examined lung and lung-associated lymph nodes derived from infant and pediatric organ donors (0–13 years) by confocal immunofluorescence and high dimensional flow cytometry. We identified early formation of bronchial associated lymphoid tissue (BALT) where active immune responses are initiated. At 8 days of life, few immune cells were present around the airways. By 5 months old, we start to observe BALT formation. However, BALT lose their structure with aging and are mostly absent by 10 years of age with CD4 memory T cells dominating the population around the central airways. Germinal centers are seen in 50–60% of BALT during the first two years of life. The percentage of BALT with germinal centers decreases over age, while germinal center formation in lung lymph nodes is maintained throughout infancy and childhood. Flow cytometry data shows seeding of transitional and immature B cells in the lung during infancy, which decreases over age. However, proportion of IgG and IgA memory B cells increases significantly over age both in the lung and lung lymph nodes. The frequency of naïve B cells is stable throughout childhood in both sites. Our results suggest that localized tertiary lymphoid structures in pediatric lungs may be an important mechanism for mobilizing rapid in situ protection during the first few years of life when memory T cells and B cells are not fully established. Supported by grants listed below: “Human Atlas of Neonatal Development and Early Life-Immunity (HANDEL-I)”(award Number 2018PG-T1D071 The Leona M. and Harry B. Helmsley Charitable Trust) “Immunobiology and alveolar physiology of the aging lung” (U01 HL145547, NIH/NHLBI )

Loss of ADAM17 from macrophages induces ST2+ T regulatory cells that limit obesity-induced metabolic inflammation in mice through changes in both membrane and soluble TNF

Abstract Obesity is known to contribute to changes in immune cells, cytokines and metabolism. Secreted TNF (sTNF) levels are directly correlated in obesity with weight gain and morbidity, as well as metabolic dysregulation. ADAM17 cleaves transmembrane TNF (mTNF) into its soluble form. This is well defined, but the mechanism behind the regulation of TNF, the source of TNF, as well as the downstream action of TNF is less clear. Our data showed that mice with ADAM17 deleted from the myeloid lineage (ADAM17LysM) had a significant metabolic advantage as illustrated by an increase in glucose tolerance and decrease in body weight. Immunophenotyping of the fatpad of these mice using high dimensional flow cytometry after high fat diet (HFD) feeding showed an increase in activated ST2+ T regulatory cells (Tregs). Based on these findings, we hypothesized that modulation of TNF on macrophages through loss of ADAM17, helps maintain a healthy metabolic state through recruitment and activation of ST2+ Treg cells that limit metabolic dysregulation. Next, we showed that the accumulation and activation of these Tregs occurred through two separate mechanistic actions of TNF. First, the loss of sTNF production from macrophages decreased soluble ST2 (sST2) production by adipocytes. This loss of sST2 augments ST2+ Treg recruitment and expansion in the fatpad due to increased bioavailable IL-33. These experiments were controlled using a myeloid-specific knockout of TNF. Second, utilizing TNFR blocking antibodies, we demonstrated that ST2+ Treg activation was dependent on macrophage mTNF acting through TNFR2. Supported by grants from NIH (R56 AI139658 and R01 AI018697)

Defining a functionally distinct, lineage dependent B1 cell population in Nippostrongylus brasiliensis infection

Abstract Nippostrongylus brasiliensis (Nb) is the strongest natural inducer of IgE. Despite this fact, asthma rates have an inverse correlation in countries endemic with parasitic infection. Our lab as well as others have sought to explain this phenomenon with little success. The mechanism behind this relationship is complicated by the fact that two different lineages of B cells, that are difficult to distinguish, are capable of making IgE. These B cell populations, B1 cells and B2 cells, have been classically separated using cell surface markers, but our data shows that these markers do not truly define these populations. Our lab has previously shown that IgE, using classical separation of these B cells, have functional differences in a Nb response. Current work shows that these populations have increased plasticity in a location dependent manner. High dimensional flow cytometry analysis of B cell populations, before and after Nb infection, illustrate this phenomenon. Using a lineage specific mouse model, reconstituted with fetal derived B cells that secrete FLAG-tagged IgE, we demonstrate that fetal derived B1 cells are not responsible for IgE production in Nb infection. However, hematopoietic cells expressing B1 markers are a significant source for this IgE. These data support a functionally distinct B cell population that is hematopoietic derived and has been previously classified as B1 cells. Supported by grants from the NIH-NIAID (R56 AI139658-01AI)

Expanding the use of clustering and dimensionality reduction in high parameter flow cytometry data through machine learning for novel samples.

Abstract High parameter flow cytometry is a highly utilized tool for accurate immunophenotyping and diagnostics in immunology, oncology, and many other disciplines. Over the past decade, several methods have been developed for automated clustering and dimensionality reduction of high parameter flow cytometry data which has sped up and simplified the discovery of cell populations not observed by manual gating strategies. However, the input and output of such tools are stochastic in nature, thus making their results difficult to reuse with novel samples. To address this challenge, we present a method utilizing machine learning to predict cluster labels and dimensionality reduction coordinates on novel samples. For proof of principle, we utilized high parameter (22 marker) flow cytometry data which examines myeloid hematopoiesis on bone marrow aspirate samples. Training data for machine learning consisted of pooled, normal, bone marrow. Phenograph was used for initial population clustering and UMAP for dimensionality reduction. A random forest model was found to be most accurate in predicting Phenograph clusters (98%) on novel data while a k-nearest neighbors (knn) model was found most accurate for UMAP coordinate prediction. The utility of this model was observed by examining acute myeloid leukemia with aberrant immunophenotypes, which were not included in the training data set. For these samples, predicted clusters and UMAP coordinates correlated with early progenitor populations from the training set. This approach allows for a de novo sample clustering and dimensionality reduction assignment onto an already established and characterized model, allowing for rapid, automated interpretation of high dimensional flow cytometry data. Supported by Cedars-Sinai Pathology and Laboratory Medicine Minigrant

Challenges in contactless inductive flow tomography for Rayleigh--Bénard convection cells

Contactless inductive flow tomography (CIFT) can reconstruct the complex 3-dimensional flow structure of the large-scale circulation in liquid metal filled Rayleigh-Bénard (RB) convection cells. The method relies on the precise measurement of weak magnetic fields induced by currents in the conducting liquid arising from the fluid motion in combination with primary excitation fields. The velocity distribution is reconstructed from the magnetic field measurements by solving a linear inverse problem using the Tikhonov regularization and L-curve method. A number of technical challenges have to be overcome to reach the desired accuracy of the measurement signals. In this paper we will describe our design of a new CIFT set-up for a large RB vessel with a diameter of 320 mm and a height of 640 mm. We outline the major factors perturbing the measurement signal of several tens of nanoteslas and describe solutions to decrease mechanical drifts by thermal expansion to a sub-critical level to enable CIFT measurements for high-Rayleigh number flows. Figs 5, Refs 16.

Influence of Internal Fins and Nanoparticles on Heat Transfer Enhancement Through a Parabolic Trough Solar Collector

Current article presents a numerical investigation for three dimensional turbulent flow using the MCRT method to simulate solar radiations as a heat flux and the finite volume method in Ansys Fluent to simulate the equations. The fluid in absorber is a synthetic oil having eight hundred index mixed with Aluminium Oxide nanoparticles to enhance the heat transfer process. The study comparing different cases, including different numbers of longitudinal fins assembled inside the absorber with two arrangements and three particular Reynolds number in addition to the testing concentration ratio of the heat flux using the MCRT method. The impact of using three different numbers of fins (2, 4 and 6) at two different arrangements ("a" and "b") were presented. The three Reynolds number used was (18600, 23000 and 28000). Two Rim angles of the collector are tested (80o) and (120o), results showed that (120º) was achieved high outlet temperature with a concentration ratio (CR=82.47). The effects on outlet temperature, friction factor, Nusselt number, and then on the performance evaluation criterion (PEC) of the absorber tube were displayed. The results of the study proved that using nanofluid and finned absorber can increase the absorber hydrothermal performance and using (6) fins of arrangement "b" shows better performance in terms of heat transfer than arrangement "a".

Spectral flow cytometric FRET: Towards a hyper dimensional flow cytometry.

Spectral flow cytometric FRET: Towards a hyper dimensional flow cytometry.

128: DECIPHERING THE IMMUNOLOGICAL DETERMINANTS OF RESPONSE TO NEOADJUVANT CHEMO-RADIATION IN ESOPHAGEAL ADENOCARCINOMA

Abstract Background and aim The standard therapy for esophageal adenocarcinoma (EAC) is pre-operative neoadjuvant chemo-radiation (NACR) and surgery. Less that 30% of patients achieve a pathological complete response (pCR) and increased 5-year survival after NACR. Understanding the mechanisms of response to NACR is pivotal to better stratify patients and inform the design of more efficacious therapies. Cancer progression partly depends on defective immune surveillance, and the presence of tumor infiltrating T lymphocytes (TILs) is associated with better prognosis of several malignancies. We hypothesize that NACR induces immunogenic cell death that stimulates immune responses against tumor neoantigens (TNAs), derived from cancer somatic mutations, in the responders. We thus compared responders and non-responders for tumor immune contexture, immune molecular pathways, circulating immune markers and TNAs-specific T cells responses. Methods Pre-NACR tumor biopsies prospectively collected from consecutive EAC patients were subjected to DNA whole exome and RNA sequencing, high dimensional (HD) multiparametric flow cytometry and immune contexture analysis by histology and by proteome digital spatial profiling (n = 53 targets), while their peripheral blood mononuclear cells and plasma collected pre- and post- NACR were analyzed by HD flow cytometry and cytokine multiplexing assay respectively. Results Treatment-naïve EACs of NACR responders showed higher TNA load and enriched immune signatures compared to non-responders. Moreover, pre-treatment EACs of responders demonstrate augmented effector T cell infiltration and reduced Treg cells and M2-like pro-tumoral macrophages. High M2-like macrophages score associated with lower overall survival. Increased frequencies of circulating myeloid suppressor populations were detected both at baseline and after NACR in non-responder patients. These observations were associated with circulating levels of n = 30 cytokines/chemokines and with spatial expression of immune markers in tumor biopsies. Conclusion Collectively, these results support pre-existing immune-mediated mechanisms of anti-tumor response stimulated by NACR in the fraction of responder EAC patients, suggesting possible ways to stratify patients and direct them to more tailored neoadjuvant and/or adjuvant treatments, possibly in combination with personalized immunotherapy approaches.