Engineering topics

Hayes, Brandon

Publications and source records attributed to Hayes, Brandon.

4 records

DOE OSTI2024

PpIX‐enabled fluorescence‐based detection and photodynamic priming of platinum‐resistant ovarian cancer cells under fluid shear stress

Over 75% percent of ovarian cancer patients are diagnosed with advanced-stage disease characterized by unresectable intraperitoneal dissemination and the presence of ascites, or excessive fluid build-up within the abdomen. Conventional treatments include cytoreductive surgery followed by multi-line platinum and taxane chemotherapy regimens. Despite an initial response to treatment, over 75% of patients with advanced-stage ovarian cancer will relapse and succumb to platinum-resistant disease. Recent evidence suggests that fluid shear stress (FSS), which results from the movement of fluid such as ascites, induces epithelial-to-mesenchymal transition and confers resistance to carboplatin in ovarian cancer cells. This study demonstrates, for the first time, that FSS-induced platinum resistance correlates with increased cellular protoporphyrin IX (PpIX), the penultimate downstream product of heme biosynthesis, the production of which can be enhanced using the clinically approved pro-drug aminolevulinic acid (ALA). These data suggest that, with further investigation, PpIX could serve as a fluorescence-based biomarker of FSS-induced platinum resistance. Additionally, this study investigates the efficacy of PpIX-enabled photodynamic therapy (PDT) and the secretion of extracellular vesicles under static and FSS conditions in Caov-3 and NIH:OVCAR-3 cells, two representative cell lines for high-grade serous ovarian carcinoma (HGSOC), the most lethal form of the disease. FSS induces resistance to ALA-PpIX-mediated PDT, along with a significant increase in the number of EVs. Finally, the ability of PpIX-mediated photodynamic priming (PDP) to enhance carboplatin efficacy under FSS conditions is quantified. These preliminary findings in monolayer cultures necessitate additional studies to determine the feasibility of PpIX as a fluorescence-based indicator, and mediator of PDP, to target chemoresistance in the context of FSS.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2024

The Liquid Jet Endstation for Hard X-ray Scattering and Spectroscopy at the Linac Coherent Light Source

The ability to study chemical dynamics on ultrafast timescales has greatly advanced with the introduction of X-ray free electron lasers (XFELs) providing short pulses of intense X-rays tailored to probe atomic structure and electronic configuration. Fully exploiting the full potential of XFELs requires specialized experimental endstations along with the development of techniques and methods to successfully carry out experiments. The liquid jet endstation (LJE) at the Linac Coherent Light Source (LCLS) has been developed to study photochemistry and biochemistry in solution systems using a combination of X-ray solution scattering (XSS), X-ray absorption spectroscopy (XAS), and X-ray emission spectroscopy (XES). The pump–probe setup utilizes an optical laser to excite the sample, which is subsequently probed by a hard X-ray pulse to resolve structural and electronic dynamics at their intrinsic femtosecond timescales. The LJE ensures reliable sample delivery to the X-ray interaction point via various liquid jets, enabling rapid replenishment of thin samples with millimolar concentrations and low sample volumes at the 120 Hz repetition rate of the LCLS beam. This paper provides a detailed description of the LJE design and of the techniques it enables, with an emphasis on the diagnostics required for real-time monitoring of the liquid jet and on the spatiotemporal overlap methods used to optimize the signal. Additionally, various scientific examples are discussed, highlighting the versatility of the LJE.

EXAFS↗

DOE OSTI2024

Tunable Metamaterials for Impact Mitigation

Traditional methods of shielding fragile goods and human tissues from impact energy rely on isotropic foam materials. The mechanical properties of these foams are inferior to an emerging class of metamaterials called plate lattices, which have predominantly been fabricated in simple 2.5-dimensional geometries using conventional methods that constrain the feasible design space. Here in this work, additive manufacturing is used to relax these constraints and realize plate lattice metamaterials with nontrivial, locally varying geometry. The limitations of traditional computer-aided design tools are circumvented and allow the simulation of complex buckling and collapse behaviors without a manual meshing step. By validating these simulations against experimental data from tests on fabricated samples, sweeping exploration of the plate lattice design space is enabled. Numerical and experimental tests demonstrate plate lattices absorb up to six times more impact energy at equivalent densities relative to foams and shield objects from impacts ten times more energetic while transmitting equivalent peak stresses. In contrast to previous investigations of plate lattice metamaterials, designs with nonuniform geometric prebuckling in the out-of-plane direction is explored and showed that these designs exhibit 10% higher energy absorption efficiency on average and 25% higher in the highest-performing design.

36 MATERIALS SCIENCE↗

DOE OSTI2023

Structural insights into functional properties of the oxidized form of cytochrome c oxidase

Abstract Cytochrome c oxidase (C c O) is an essential enzyme in mitochondrial and bacterial respiration. It catalyzes the four-electron reduction of molecular oxygen to water and harnesses the chemical energy to translocate four protons across biological membranes. The turnover of the C c O reaction involves an oxidative phase, in which the reduced enzyme (R) is oxidized to the metastable O H state, and a reductive phase, in which O H is reduced back to the R state. During each phase, two protons are translocated across the membrane. However, if O H is allowed to relax to the resting oxidized state (O), a redox equivalent to O H , its subsequent reduction to R is incapable of driving proton translocation. Here, with resonance Raman spectroscopy and serial femtosecond X-ray crystallography (SFX), we show that the heme a 3 iron and Cu B in the active site of the O state, like those in the O H state, are coordinated by a hydroxide ion and a water molecule, respectively. However, Y244, critical for the oxygen reduction chemistry, is in the neutral protonated form, which distinguishes O from O H , where Y244 is in the deprotonated tyrosinate form. These structural characteristics of O provide insights into the proton translocation mechanism of C c O.

36 MATERIALS SCIENCE↗