Keynote Address: Dr. Kori Schake

2022 United Sates Strategic Command Academic Alliance Conference and Workshop, Mark 30-April 1, 2022, Conducted via Zoo

Blood Flow Regulates Atherosclerosis Progression and Regression

Atherosclerosis is the most prevalent pathology of cardiovascular disease with no known cure. Despite the many systemic risk factors for atherosclerosis, plaques do not form randomly in the vasculature. Instead, they form around bifurcations and the inner curvature of highly curving arterial segments that contain so-called disturbed blood flow that is low in magnitude and multidirectional over the cardiac cycle. Conversely, straight, non-bifurcated arterial segments that contain moderate-to-high and unidirectional (i.e., normal) blood flow are protected from plaque development. Thus, blood flow is a key regulator of atherosclerosis that may be able to be leveraged to develop new therapeutics. Towards this end, we performed two studies using a mouse model of atherosclerosis where a blood flow-modifying cuff was placed around the left carotid artery to induce disturbed blood flow and, in turn, plaque development. In the first study, we evaluated the hypothesis that injected nanoparticles had different accumulation kinetics in different types of disturbed flow (low versus multidirectional). We found that the blood flow profile did not affect accumulation, but the resultant plaque phenotype did. This suggests that nanoparticles could be used to target certain plaque types. In the second study, we evaluated the hypothesis that restored normal blood flow in atherosclerotic arteries promotes plaque stabilization. Our findings supported this hypothesis and also showed that the combination of normal blood flow and atorvastatin produced additive beneficial effects that led to plaque regression. This result suggests that mechanical stimuli can be therapeutic. Since the endothelium directly senses blood flow and plays a key role in atherosclerosis development, we finally characterized how different flow profiles affect atheroprotective versus atherogenic endothelial signaling molecules. Ultimately, this work provides a foundation for the development of a new therapeutic for atherosclerosis based on the beneficial effects of normal blood flow. Advisor: Ryan M. Pedrig

Concept for improving the form measurement results of aspheres and freeform surfaces in a tilted-wave interferometer

Accurate and flexible form measurements for aspherical and freeform surfaces are in high demand, and non-null-test interferometric methods such as tilted-wave interferometry have gained attention as a promising response to this need. Interferometric methods, however, display ambiguities between the measurement of certain form errors and the misalignment of the measured specimen. Therefore, improved knowledge of the absolute measurement position of the specimen in relation to the interferometer setup may improve the form measurement result. In this work, we propose a concept that uses a white light interferometer to measure the absolute distance between a transparent specimen's surface and the interferometer's objective and present preparatory data to qualify the white light interferometer for the improvement of tilted-wave interferometer measurements.</p

Gape:Body Size Relationship for Smallmouth Bass

The types and sizes of prey fishes consumed by predatory fish often are limited by gape dimensions of the predator (Slaughter and Jacobson 2008). In general, the size of prey consumed is positively related to predator size when prey are available across a wide range of sizes (Werner and Hall 1974). Opportunistic predators with large gape dimensions, such as smallmouth bass (Micropterus dolomieu), may consume a wide range of prey types and sizes, thereby exerting top-down influences on prey population dynamics and potentially restructuring aquatic communities (e.g., Werner and Hall 1974, Jackson 2002). Although feeding ecology of smallmouth bass varies with location and prey availability, they typically undergo several ontogenetic diet shifts throughout their development. After yolk sac depletion and as smallmouth bass increase in size from larvae to juveniles (~50 mm total length; TL), targeted prey typically proceeds from microcrustaceans (e.g., copepods) to larger zooplankters (e.g., cladocerans) to macroinvertebrates (e.g., ephemeropterans; Brown et al. 2009). Opportunistic feeding behaviors become more apparent during the juvenile stage (TL \u3e 50 mm) when smallmouth bass begin to consume readily available aquatic macroinvertebrates and prey fishes (Clady 1974, Easton and Orth 1992). Studies evaluating adult feeding ecology highlight the importance of crayfish (Gangl et al. 1997, Liao et al. 2002, Bacula 2009) but also reveal the piscivorous nature of smallmouth bass in some locations (e.g., Jackson 2002, Liao et al. 2002, Bacula 2009, Wuellner et al. 2010)

The US Commitments to NATO in the Post-Cold War Period - A Case Study on Libya

The recent history of the US commitment to NATO has been dominated by economic pressures, squabbles over NATO’s military performance in Afghanistan, and the apparent American preference for ‘leading from behind’ in Libya. The case study on Libya will be especially important in exploring the Obama administration’s understanding of the purpose of NATO in the context of current economic pressures, domestic US debates about post-War on Terror interventions, and of increasing American preoccupation with Pacific (rather than European) security. In the case of Libya, the US apparently hesitated to unfold military operations against Libyan military targets. It seems to be the first time that the US followed rather than led its European allies to a campaign. The reason why the US was reluctant to intervene in Libya at the very beginning; why it changed its mind to join the operation later; and why it transferred the Libyan mission to NATO and adopted the strategy of ‘leading from behind’, reflected on not only the redefinition of ‘American way of war’, but also the future of NATO

Smooth muscle cells affect differential nanoparticle accumulation in disturbed blood flow-induced murine atherosclerosis

Atherosclerosis is a lipid-driven chronic inflammatory disease that leads to the formation of plaques in the inner lining of arteries. Plaques form over a range of phenotypes, the most severe of which is vulnerable to rupture and causes most of the clinically significant events. In this study, we evaluated the efficacy of nanoparticles (NPs) to differentiate between two plaque phenotypes based on accumulation kinetics in a mouse model of atherosclerosis. This model uses a perivascular cuff to induce two regions of disturbed wall shear stress (WSS) on the inner lining of the instrumented artery, low (upstream) and multidirectional (downstream), which, in turn, cause the development of an unstable and stable plaque phenotype, respectively. To evaluate the influence of each WSS condition, in addition to the final plaque phenotype, in determining NP uptake, mice were injected with NPs at intermediate and fully developed stages of plaque growth. The kinetics of artery wall uptake were assessed in vivo using dynamic contrast-enhanced magnetic resonance imaging. At the intermediate stage, there was no difference in NP uptake between the two WSS conditions, although both were different from the control arteries. At the fully-developed stage, however, NP uptake was reduced in plaques induced by low WSS, but not multidirectional WSS. Histological evaluation of plaques induced by low WSS revealed a significant inverse correlation between the presence of smooth muscle cells and NP accumulation, particularly at the plaque-lumen interface, which did not exist with other constituents (lipid and collagen) and was not present in plaques induced by multidirectional WSS. These findings demonstrate that NP accumulation can be used to differentiate between unstable and stable murine atherosclerosis, but accumulation kinetics are not directly influenced by the WSS condition. This tool could be used as a diagnostic to evaluate the efficacy of experimental therapeutics for atherosclerosis

Ultrafiltration evaluation with depleted uranium oxide

Scientists at the Los Alamos National Laboratory Plutonium Facility are using electrodissolution in neutral to alkaline solutions to decontaminate oralloy parts that have surface plutonium contamination. Ultrafiltration of the electrolyte stream removes precipitate so that the electrolyte stream to the decontamination fixture is precipitate free. This report describes small-scale laboratory ultrafiltration experiments that the authors performed to determine conditions necessary for full-scale operation of an ultrafiltration module. Performance was similar to what they observed in the ferric hydroxide system. At 12 psi transmembrane pressure, a shear rate of 12,000 sec{sup {minus}1} was sufficient to sustain membrane permeability. Ultrafiltration of uranium(VI) oxide appears to occur as easily as ultrafiltration of ferric hydroxide. Considering the success reported in this study, the authors plan to add ultrafiltration to the next decontamination system for oralloy parts

Synthetic, structural, spectroscopic and theoretical study of a Mn(III)-Cu(II) dimer containing a Jahn-Teller compressed Mn ion

The heterobimetallic complex [Cu(II)Mn(III)(L)(2)(py)(4)](ClO4)center dot EtOH (1) built using the pro-ligand 2,2'-biphenol (LH2), contains a rare example of a Jahn-Teller compressed Mn(III) centre. Dc magnetic susceptibility measurements on 1 reveal a strong antiferromagnetic exchange between the Cu(II) and Mn(III) ions mediated through the phenolate O-atoms (J = -33.4 cm(-1)), with magnetisation measurements at low temperatures and high fields suggesting significant anisotropy. Simulations of high-field and high frequency powder EPR data suggest a single-ion anisotropy D-Mn(III) = +4.45 cm(-1). DFT calculations also yield an antiferromagnetic exchange for 1, though the magnitude is overestimated (J(DFT) = -71 cm(-1)). Calculations reveal that the antiferromagnetic interaction essentially stems from the Mn(d(x2-y2))-Cu(d(x2-y2)) interaction. The computed single-ion anisotropy and cluster anisotropy also correlates well with experiment. A larger cluster anisotropy for the S = 3/2 state compared to the single-ion anisotropy of Mn(III) is rationalised on the basis of orbital mixing and various contributions that arise due to the spin-orbit interaction