owen Richfield - Academia.edu (original) (raw)

Papers by owen Richfield

Nature communications, May 18, 2024

Journal of the American Society of Nephrology, Oct 1, 2020

Frontiers in physiology, Jun 20, 2024

Journal of Controlled Release, Aug 1, 2023

Nature Communications

Vascular endothelial cells (ECs) play a central role in the pathophysiology of many diseases. The... more Vascular endothelial cells (ECs) play a central role in the pathophysiology of many diseases. The use of targeted nanoparticles (NPs) to deliver therapeutics to ECs could dramatically improve efficacy by providing elevated and sustained intracellular drug levels. However, achieving sufficient levels of NP targeting in human settings remains elusive. Here, we overcome this barrier by engineering a monobody adapter that presents antibodies on the NP surface in a manner that fully preserves their antigen-binding function. This system improves targeting efficacy in cultured ECs under flow by >1000-fold over conventional antibody immobilization using amine coupling and enables robust delivery of NPs to the ECs of human kidneys undergoing ex vivo perfusion, a clinical setting used for organ transplant. Our monobody adapter also enables a simple plug-and-play capacity that facilitates the evaluation of a diverse array of targeted NPs. This technology has the potential to simplify and po...

2016 IEEE International Conference on Bioinformatics and Biomedicine (BIBM), 2016

Kernel and Multiple Kernel Canonical Correlation Analysis (CCA) are employed to classify schizoph... more Kernel and Multiple Kernel Canonical Correlation Analysis (CCA) are employed to classify schizophrenic and healthy patients based on their SNPs, DNA Methylation and fMRI data. Kernel and Multiple Kernel CCA are popular methods for finding nonlinear correlations between high-dimensional datasets. Data was gathered from 183 patients, 79 with schizophrenia and 104 healthy controls. Kernel and Multiple Kernel CCA represent new avenues for studying schizophrenia, because, to our knowledge, these methods have not been used on these data before. Classification is performed via k-means clustering on the kernel matrix outputs of the Kernel and Multiple Kernel CCA algorithm. Accuracies of the Kernel and Multiple Kernel CCA classification are compared to that of the regularized linear CCA algorithm classification, and are found to be significantly more accurate. Both algorithms demonstrate maximal accuracies when the combination of DNA methylation and fMRI data are used, and experience lower accuracies when the SNP data are incorporated.

Hypertension, 2020

Angiotensin II (Ang II)-induced hypertension increases afferent and efferent arteriole resistance... more Angiotensin II (Ang II)-induced hypertension increases afferent and efferent arteriole resistances via the actions of Ang II on the AT1 receptor. In addition to the increased interstitial levels of Ang II, the increased arterial pressure increases interstitial ATP concentrations which act on the purinergic receptors P2X1 and P2X7, to constrict the AA, preventing increases in plasma flow and single nephron GFR (SNGFR). Blockade of the P2 receptors also mitigates the effects of Ang II, thus increasing blood flow and SNGFR, but the resulting increases in mechanical stresses (shear stress and circumferential hoop stress) on the glomerular microvasculature have not been quantified. A mathematical microvascular hemodynamic glomerular model was developed to simulate blood flow and plasma filtration at each of 320 capillary segments in an anatomically-accurate rat glomerular capillary network topology. Afferent and efferent arteriole resistances and network hydraulic conductivity were adjus...

Hypertension, 2019

The 5/6-nephrectomy (5/6 Nx) model of renal mass reduction shows an increased glomerular pressure... more The 5/6-nephrectomy (5/6 Nx) model of renal mass reduction shows an increased glomerular pressure (ΔP) and afferent plasma flow (Q a ) in the remaining glomeruli. These hemodynamic consequences are assumed to increase glomerular capillary wall circumferential hoop stress (HS) and shear stress (SS), respectively. Due to a lack of anatomically-accurate mathematical models of the glomerulus, the actual magnitudes of SS and HS in the entire network of glomerular capillaries remain uncertain in 5/6-Nx. These forces are of significance due to the sensitivity of endothelial cells to SS and podocytes to HS. We developed a mathematical model of blood flow through an anatomically-accurate rat glomerular capillary network to estimate the magnitudes of SS and HS on the glomerular capillary walls in 5/6-Nx. Filtration rates, wall HS and wall SS were calculated for each capillary segment of the network based on parameters obtained from a micropuncture study using normal rats and rats with 5/6-Nx ...

SPORA: A Journal of Biomathematics, 2016

Sperm of certain species engage in cooperative swimming behaviors, which result in differences in... more Sperm of certain species engage in cooperative swimming behaviors, which result in differences in velocity and efficiency of swimming as well as ability to effectively fertilize the egg. In particular, Monodelphis domestica is a species of opossum whose sperm often swim cooperatively as a pair, with heads fused together. In order to understand the empirical effects of cooperative swimming behaviors, we propose a simple preferred-curvature-based model to model individual and paired sperm using the method of regularized Stokeslets to model the viscous fluid environment. The effects of swimming freely versus paired swimming, phase relationship, and the angle at which sperm heads are fused are investigated. Results are consistent with previous modeling work for free swimmers. Paired (fused) swimming results also compare well with experimental work and provide evidence for optimal geometrical configurations. This indicates that there may be a fluid mechanical advantage to such cooperative motility behaviors in sperm swimming.

F1000 - Post-publication peer review of the biomedical literature, 2018

Cooperative swimming behavior in sperm is a phenomenon observed in many species of rodents and ma... more Cooperative swimming behavior in sperm is a phenomenon observed in many species of rodents and marsupials. These behaviors involve swimming in pairs or groups, often with a mechanical link between individuals. In particular, some species of opossum have sperm often swim cooperatively as a pair, with heads fused together. While this behavior has been well-documented, it is unknown how it contributes to fertilization potential. In some experimental work, it has been shown that groups swim faster than individuals. On the other hand, a significant portion of the sperm engaged in collective swimming are rendered unable to fertilize the oocyte because of damage caused by the collective swimming itself. In this talk, we will introduce an undergraduate research project investigating the potential advantages to cooperative swimming behavior in low Reynolds number (viscous) fluid flow. We will highlight our mathematical and computational methodology, as well as how to engage undergraduates with minimal computational or physics background. Interestingly, our results indicate there are fluid mechanical advantages for cooperative swimming behaviors that coincide with similar geometries observed in biological studies. We postulate these results may provide evidence for an evolutionary advantage to cooperative swimming in sperm.

Fluids

We derive a new computational model for the simulation of viscous incompressible flows bounded by... more We derive a new computational model for the simulation of viscous incompressible flows bounded by a thin, flexible, porous membrane. Our approach is grid-free and models the boundary forces with regularized Stokeslets. The flow across the porous membranes is modeled with regularized source doublets based on the notion that the flux velocity across the boundary can be viewed as the flow induced by a fluid source/sink pair with the sink on the high-pressure side of the boundary and magnitude proportional to the pressure difference across the membrane. Several validation examples are presented that illustrate how to calibrate the parameters in the model. We present an example consisting of flow in a closed domain that loses volume due to the fluid flux across the permeable boundary. We also present applications of the method to flow inside a channel of fixed geometry where sections of the boundary are permeable. The final example is a biological application of flow in a capillary with ...