Master of Science

thesisA standard lumped parameter model for an inertial vibration energy harvester consists of a proof mass, spring, and damper(s). This model can also be described with a proof mass, viscous damping element for parasitic mechanical losses, and a generalized transducer that applies some force to the mass damper system. The transducer may contain restorative spring elements and energy extraction elements to harvest power. Currently the framework to relate vibration input to an optimal transducer architecture does not exist. Previous work has shown that for some inputs nonlinear transducer architectures can result in an increased power output. This paper outlines a mathematical framework needed in order to find the optimal transducer architecture for a given vibration input. This framework defines the theoretical upper limit that any inertial transducer can harvest from a given vibration input in the presence of viscous mechanical damping. This framework is then applied to three cases of standard input types. The first application is a single sinusoid input. The transducer architecture found is the expected result, a linear spring with matched resonance to the input, and an energy extraction element, that behaves as a linear viscous damper, with matched impedance to the mechanical damping. The second application of this framework is an input of two sinusoids both having equal magnitude but different frequencies. The resulting optimal transducer is dependent on the difference in the frequencies of the two signals. This optimal transducer is often not realizable with a passive system, as it is inherently time dependent. For all cases of frequency separation between the two sinusoidal inputs, the upper limit for the energy generated is found to be twice that of a linear harvester tuned to the lower of the two frequencies. The third application is for an input whose frequency changes linearly in time (i.e. a swept sinusoid). The optimal transducer architecture for this input is found to be completely time dependent. However for the case when the change in the input frequency is much slower than the period of the system, the transducer can be approximated by a linear spring whose stiffness changes in time

Actin polymerization stabilizes α4β1 integrin anchors that mediate monocyte adhesion

Leukocytes arrested on inflamed endothelium via integrins are subjected to force imparted by flowing blood. How leukocytes respond to this force and resist detachment is poorly understood. Live-cell imaging with Lifeact-transfected U937 cells revealed that force triggers actin polymerization at upstream α4β1 integrin adhesion sites and the adjacent cortical cytoskeleton. Scanning electron microscopy revealed that this culminates in the formation of structures that anchor monocyte adhesion. Inhibition of actin polymerization resulted in cell deformation, displacement, and detachment. Transfection of dominant-negative constructs and inhibition of function or expression revealed key signaling steps required for upstream actin polymerization and adhesion stabilization. These included activation of Rap1, phosphoinositide 3-kinase γ isoform, and Rac but not Cdc42. Thus, rapid signaling and structural adaptations enable leukocytes to stabilize adhesion and resist detachment forces

Executive summary: heart disease and stroke statistics--2013 update: a report from the American Heart Association.

Each year, the American Heart Association (AHA), in conjunction with the Centers for Disease Control and Prevention, the National Institutes of Health, and other government agencies, brings together the most up-to-date statistics on heart disease, stroke, other vascular diseases, and their risk factors and presents them in its Heart Disease and Stroke Statistical Update*The Statistical Update is a valuable resource for researchers, clinicians, healthcare policy makers, media professionals, the lay public, and many others who seek the best national data available on heart disease, stroke, and other cardiovascular disease-related morbidity and mortality and the risks, quality of care, medical procedures and operations, and costs associated with the management of these diseases in a single document*Indeed, since 1999, the Statistical Update has been cited \u3e10 500 times in the literature, based on citations of all annual versions*In 2011 alone, the various Statistical Updates were cited ≈1500 times (data from ISI Web of Science)*In recent years, the Statistical Update has undergone some major changes with the addition of new chapters and major updates across multiple areas, as well as increasing the number of ways to access and use the information assembled*For this year\u27s edition, the Statistics Committee, which produces the document for the AHA, updated all of the current chapters with the most recent nationally representative data and inclusion of relevant articles from the literature over the past year*This year\u27s edition also implements a new chapter organization to reflect the spectrum of cardiovascular health behaviors and health factors and risks, as well as subsequent complicating conditions, disease states, and outcomes*Also, the 2013 Statistical Update contains new data on the monitoring and benefits of cardiovascular health in the population, with additional new focus on evidence-based approaches to changing behaviors, implementation strategies, and implications of the AHA\u27s 2020 Impact Goals*Below are a few highlights from this year\u27s Update . © 2013 American Heart Association, Inc

Executive summary: heart disease and stroke statistics--2014 update: a report from the American Heart Association.

Each year, the American Heart Association (AHA), in conjunction with the Centers for Disease Control and Prevention, the National Institutes of Health, and other government agencies, brings together the most up-to-date statistics on heart disease, stroke, other vascular diseases, and their risk factors and presents them in its Heart Disease and Stroke Statistical Update. The Statistical Update is a critical resource for researchers, clinicians, healthcare policy makers, media professionals, the lay public, and many others who seek the best available national data on heart disease, stroke, and other cardiovascular disease-related morbidity and mortality and the risks, quality of care, use of medical procedures and operations, and costs associated with the management of these diseases in a single document. Indeed, since 1999, the Statistical Update has been cited >10 500 times in the literature, based on citations of all annual versions. In 2012 alone, the various Statistical Updates were cited ≈3500 times (data from Google Scholar). In recent years, the Statistical Update has undergone some major changes with the addition of new chapters and major updates across multiple areas, as well as increasing the number of ways to access and use the information assembled. For this year's edition, the Statistics Committee, which produces the document for the AHA, updated all of the current chapters with the most recent nationally representative data and inclusion of relevant articles from the literature over the past year. This year's edition includes a new chapter on peripheral artery disease, as well as new data on the monitoring and benefits of cardiovascular health in the population, with additional new focus on evidence-based approaches to changing behaviors, implementation strategies, and implications of the AHA's 2020 Impact Goals. Below are a few highlights from this year's Update. © 2013 American Heart Association, Inc

Detectable Clonal Mosaicism from Birth to Old Age and its Relationship to Cancer

Clonal mosaicism for large chromosomal anomalies (duplications, deletions and uniparental disomy) was detected using SNP microarray data from over 50,000 subjects recruited for genome-wide association studies. This detection method requires a relatively high frequency of cells (>5–10%) with the same abnormal karyotype (presumably of clonal origin) in the presence of normal cells. The frequency of detectable clonal mosaicism in peripheral blood is low (<0.5%) from birth until 50 years of age, after which it rises rapidly to 2–3% in the elderly. Many of the mosaic anomalies are characteristic of those found in hematological cancers and identify common deleted regions that pinpoint the locations of genes previously associated with hematological cancers. Although only 3% of subjects with detectable clonal mosaicism had any record of hematological cancer prior to DNA sampling, those without a prior diagnosis have an estimated 10-fold higher risk of a subsequent hematological cancer (95% confidence interval = 6–18)

Alterations in Platelet Function and Cell-Derived Microvesicles in Recently Menopausal Women: Relationship to Metabolic Syndrome and Atherogenic Risk

A woman’s risk for metabolic syndrome (MS) increases at menopause, with an associated increase in risk for cardiovascular disease. We hypothesized that early menopause-related changes in platelet activity and concentrations of microvesicles derived from activated blood and vascular cells provide a mechanistic link to the early atherothrombotic process. Thus, platelet functions and cellular origin of blood-borne microvesicles in recently menopausal women (n = 118) enrolled in the Kronos Early Estrogen Prevention Study were correlated with components of MS and noninvasive measures of cardiovascular disease [carotid artery intima medial thickness (CIMT), coronary artery calcium (CAC) score, and endothelial reactive hyperemic index (RHI)]. Specific to individual components of the MS pentad, platelet number increased with increasing waist circumference, and platelet secretion of ATP and expression of P-selectin decreased with increasing blood glucose (p = 0.005) and blood pressure (p < 0.05), respectively. Waist circumference and systolic blood pressure were independently associated with monocyte- and endothelium-derived microvesicles (p < 0.05). Platelet-derived and total procoagulant phosphatidylserine-positive microvesicles, and systolic blood pressure correlated with CIMT (p < 0.05), but not with CAC or RHI. In summary, among recently menopausal women, specific platelet functions and concentrations of circulating activated cell membrane-derived procoagulant microvesicles change with individual components of MS. These cellular changes may explain in part how menopause contributes to MS and, eventually, to cardiovascular disease

Combined near infrared photoacoustic imaging and ultrasound detects vulnerable atherosclerotic plaque.

Atherosclerosis is an inflammatory process resulting in the deposition of cholesterol and cellular debris, narrowing of the vessel lumen and clot formation. Characterization of the morphology and vulnerability of the lesion is essential for effective clinical management. Here, near-infrared auto-photoacoustic (NIRAPA) imaging is shown to detect plaque components and, when combined with ultrasound imaging, to differentiate stable and vulnerable plaque. In an ex vivo study of photoacoustic imaging of excised plaque from 25 patients, 88.2% sensitivity and 71.4% specificity were achieved using a clinically-relevant protocol. In order to determine the origin of the NIRAPA signal, immunohistochemistry, spatial transcriptomics and spatial proteomics were co-registered with imaging and applied to adjacent plaque sections. The highest NIRAPA signal was spatially correlated with bilirubin and associated blood-based residue and with the cytoplasmic contents of inflammatory macrophages bearing CD74, HLA-DR, CD14 and CD163 markers. In summary, we establish the potential to apply the NIRAPA-ultrasound imaging combination to detect vulnerable carotid plaque and a methodology for fusing molecular imaging with spatial transcriptomic and proteomic methods