The wearing effects of being overworked and in somewhat poor health are reflected in my paintings, ceramic work, and mixed media pieces. I use old and dilapidated materials such as window frames, instrument cases, and wood to symbolically address my physical and emotional states. I reuse items from the past that show a sense of fatigue, tattered edges, and deterioration. Like these objects I felt run down, old, and at times, useless. However, I am comforted by the idea that old objects can, with some care, regain new life. I have discovered I seek my own rejuvenation through my creativity. As a means of releasing anger and frustration toward my fading health, I create assemblages of wilted flowers, encaustic hourglass forms, and mixed media teapots. I also create clay vessels that appear to be deteriorating and encapsulate objects in encaustic medium. Items that belonged to my relatives serve as a metaphor for my genetic illnesses. Searching for answers, living in the present, and maintaining hope are things I carry with me on my artistic journey to find a sense of self worth and to overcome disease.

Microcirculation has become a key factor for the study and assessment of tissue perfusion and oxygenation. Detection and assessment of the microvasculature using videomicroscopy from the oral mucosa provides a metric on the density of blood vessels in each single frame. Information pertaining to the density of these microvessels within a field of view can be used to quantitatively monitor and assess the changes occurring in tissue oxygenation and perfusion over time. Automated analysis of this information can be used for real-time diagnostic and therapeutic planning of a number of clinical applications including resuscitation. The objective of this study is to design an automated image processing system to segment microvessels, estimate the density of blood vessels in video recordings, and identify the distribution of blood flow. The proposed algorithm consists of two main stages: video processing and image segmentation. The first step of video processing is stabilization. In the video stabilization step, block matching is applied to the video frames. Similarity is measured by cross-correlation coefficients. The main technique used in the segmentation step is multi-thresholding and pixel verification based on calculated geometric and contrast parameters. Segmentation results and differences of video frames are then used to identify the capillaries with blood flow. After categorizing blood vessels as active or passive, according to the amount of blood flow, quantitative measures identifying microcirculation are calculated. The algorithm is applied to the videos obtained using Microscan Side-stream Dark Field (SDF) imaging technique captured from healthy and critically ill humans/animals. Segmentation results were compared and validated using a blind detailed inspection by experts who used a commercial semi-automated image analysis software program, AVA (Automated Vascular Analysis). The algorithm was found to extract approximately 97% of functionally active capillaries and blood vessels in every frame. The aim of this study is to eliminate the human interaction, increase accuracy and reduce the computation time. The proposed method is an entirely automated process that can perform stabilization, pre-processing, segmentation, and microvessel identification without human intervention. The method may allow for assessment of microcirculatory abnormalities occurring in critically ill and injured patients including close to real-time determination of the adequacy of resuscitation.

My love of learning, teaching, and providing creative spaces for people to connect informs my work and my life. For me, art is like life: messy, physical, and, if done with intent, beautiful. It is more about the process than the result; it is about recognizing that although we make choices, there are many things we cannot control; it is about being so present in the moment that everything else fades away. How I live, what I do, what I believe, and my art are all the same.

Tissue engineered blood vessels (TEBVs) have great potential as tools for disease modeling and drug screening. However, existing methods for fabricating TEBVs create homogenous tissue tubes, which may not be conducive to modeling focal vascular diseases such as intimal hyperplasia or aneurysm. In contrast, our lab has a unique modular system for fabricating TEBVs. Smooth muscle cells (SMCs) are seeded into an annular agarose mold, where they aggregate into vascular tissue rings, which can be stacked and fused into small diameter TEBVs. Our goal is to create a platform technology that may be used for fabricating focal vascular disease models, such as intimal hyperplasia. Because tubes are fabricated from individual ring units, each ring can potentially be customized, enabling the creation of focal changes or regions of disease along the tube length. In these studies, we first demonstrated our ability to modulate cell phenotype within individual SMC ring units using incorporated growth factor-loaded degradable gelatin microspheres. Next, we evaluated fusion of ring subunits to form composite tissue tubes, and demonstrated that cells retain their spatial positioning within individual rings during fusion. By incorporating electrospun polycaprolactone cannulation cuffs at each end, tubes were mounted on bioreactors after only 7 days of fusion to impart luminal medium flow for 7 days at a physiological shear stress of 12 dyne/cm2. We then created focal heterogeneities along the tube length by fusing microsphere-containing rings in the central region of the tube between rings without microspheres. In the future, microspheres may be used to deliver growth factors to this localized region of microsphere incorporation and induce disease phenotypes. Due to the challenges of working with primary human SMCs, we next evaluated human mesenchymal stem cells (hMSCs) as an alternative cell source to generate vascular SMCs. We evaluated the effects of microsphere-mediated platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), and transforming growth factor beta-1 (TGF-β1) delivery on ring thickness, proliferation, and contractile protein expression over a 14 day period. Finally, we created a structurally distinct region of smooth muscle within tissue tubes by fusing human aortic SMCs in a central region between hMSC rings. In summary, we developed a platform technology for creating modular tubular tissues that may be further developed into an in vitro intimal hyperplasia model. It may also be modified to model other focal vascular diseases, such as aneurysm, or to create other types of multi-tissue tubular structures, such as trachea.

Cerebral small vessel disease (SVD) is a distinct microvascular disorder that can lead to lacunar stroke, an important stroke subtype that accounts for a quarter of all ischaemic strokes. SVD is associated with imaging biomarkers such as white matter hyperintensities (WMH). The cause of SVD is largely unknown, although inflammation and blood-brain barrier failure via endothelial dysfunction have been implicated. Elevated plasma biomarkers of inflammation are associated with coronary heart disease and large vessel stroke but the role of inflammation in SVD is less well understood. Our hypothesis is that inflammation plays a role in SVD and we sought to examine this by reviewing the literature for evidence of this, and by conducting a brain imaging study of patients with a known inflammatory disease and reviewing the images for evidence of inflammation and SVD, and comparing findings with controls groups. Section A: This thesis begins with a systematic review and meta-analysis of 13 plasma biomarkers of four physiological processes (coagulation, fibrinolysis, endothelial dysfunction and inflammation) in lacunar stroke versus non-lacunar stroke (to control for having any stroke) and non-stroke (to compare to the general population). We sought to know if there were differences in these biomarkers between lacunar stroke and other stroke subtypes and non-stroke controls as a way of generating hypotheses for the disease mechanisms that might lead to lacunar stroke. Findings revealed differences in several biomarkers between lacunar stroke and healthy controls but only fibrinogen, D-dimer, von Willebrand factor and interleukin-6 were different (all significantly lower in lacunar stroke) between lacunar stroke and other stroke subtypes. There was heterogeneity between studies, including variations in the definition of lacunar stroke and most studies measured the biomarkers in the acute phase post stroke, which is potentially confounding. To further examine plasma biomarkers of inflammation and endothelial dysfunction in SVD, we used data from a prior study of mild stroke conducted at the Brain Research Imaging Centre, University of Edinburgh, UK. Lacunar stroke patients were compared to cortical stroke patients. The lacunar group had lower levels of tissue plasminogen activator independent of age, sex and vascular risk factors but we found no difference in the other plasma biomarkers. Section B: Non-resolving systemic inflammation is a feature of inflammatory autoimmune rheumatic diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). These patients are at increased risk of stroke but much knowledge relates to stroke in general; less is known about associations with stroke subtypes including SVD, or when in life stroke risk is greatest. Consequently, we sought to better understand the influence of inflammatory rheumatic diseases on stroke and SVD. The review and meta-analysis of cerebrovascular disease in rheumatic diseases showed an excess risk of stroke in RA, SLE, ankylosing spondylitis, gout and psoriasis over the general population. Meta-analyses of stroke subtypes (ischaemic and haemorrhagic) in RA and SLE showed an excess risk of stroke over the general population. Stroke risk across rheumatic diseases was highest in those aged < 50 years and reduced with ageing. We then requested data from NHS Lothian covering 15 years so that we could assess stroke, including stroke subtypes, among patients diagnosed with various arthropathies. We linked 6,613 rheumatology patients’ records with stroke admission records, grouped the various rheumatic diseases into the two main types of arthritis, inflammatory and non-inflammatory, and also compared the strokes in these rheumatology patients to general population data. There was no difference in stroke prevalence between inflammatory and degenerative (non-inflammatory) arthropathies, although the strokes occurred up to two decades earlier than in the general population. Section C: Lastly, we conducted MRI neuroimaging in patients with SLE and reviewed and meta-analysed diffusion tensor imaging (DTI) (an imaging technique used to assess sub-visible white matter microstructure damage) in SLE to place our findings into context. The research question here was to ascertain if patients with a known inflammatory disease had brain imaging evidence of SVD, and to compare findings to controls. We compared imaging markers of SVD and DTI between SLE patients and age-matched healthy controls and sought associations between the imaging biomarkers and plasma biomarkers of inflammation and endothelial dysfunction, measures of fatigue and cognition, and scores of rheumatic disease activity. Fifty-one patients were recruited. There was higher mean diffusivity in all white matter tracts versus controls indicating a diffuse increase in brain water mobility in SLE. Meta-analysis confirmed higher mean diffusivity in SLE patients versus controls. Fatigue in SLE was significantly higher than a normal reference range and was associated with depression, anxiety, higher body mass index, lower mean diffusivity and some blood markers of inflammation and endothelial dysfunction. The most fatigued were youngest which explained the association with lower mean diffusivity. Damage to the brain’s white matter microstructure may be accelerated in SLE as the age-related declines in the general population are normally seen much later in life. The aging pattern is consistent with inflammation-related microvascular-mediated brain damage where the inflammation is systemic in origin. Summary: This thesis has demonstrated an increase in SVD burden in the inflammatory rheumatic disease SLE and increased stroke risk at younger ages in other inflammatory rheumatic diseases. Thus, systemic inflammation as seen in inflammatory rheumatic diseases could have effects on the brain directly, including influencing stroke risk which is clinically noteworthy and would benefit from further testing in appropriately designed studies such as an inception cohort that follows inflammatory rheumatic patients from diagnosis, with regular brain imaging to track brain changes and correlates with inflammatory profiles and impact on cognition.

The artist discusses the concept, imagery, and research influences behind a body of work entitled What We Give, for the completion of her Bachelor of Arts Degree and undergraduate research for the Fine and Performing Arts Scholars branch of East Tennessee State University’s Honors College. The artist used this body of work to explore her personal relationships with the ocean, Aspergers, and information. Particularly, the artist’s pseudo-mystic beliefs about the ocean, her frustrations with her life struggles, and fascinations with scientific facts and libation vessels are discussed. Dysfunctionality is cited as the driving force behind the thought process of the project. Her work includes two sculptural vessels, rendered in ceramics and painted with house paint. The artist cites gastropod shells, ancient libation vessels, and contemporary artists Marcel Duchamp, Beth Cavener Stichter, and Alison Evans as inspirations.

Coronary heart disease is a prevalent issue in developed countries throughout the world. It can have crippling effects on the quality of life and even lead to mortality, in the case of myocardial infarction. Part of the problem is the lack of a robust regenerative response in mammals after injury. Zebrafish have an amazing ability to regenerate after injury, and studies have demonstrated that the regenerative response recapitulates embryonic development. Our lab previously reported the first analysis of coronary vessel development in zebrafish and demonstrated that coronary endothelial cells undergo angiogenesis to form a vascular network. The roles of perivascular cells in this process have not been examined in zebrafish. Using a transgenic reporter line marking pdgfrb expression, I found that pdgfrb is first observed in epicardium at the AV canal. At later stages of coronary vessel development, pdgfrb positive cells become localized to the perivascular region of mature vessels. I also observe that early in development, Tcf21 and pdgfrb co-express, which suggests a close relationship between the epicardium and pdgfrb+ cells. Previous findings from our lab revealed that cxcl12b+ cells localize to large coronary vessels during development. My findings reveal that pdgfrb+ marks perivascular cells of both capillaries and large coronary vessels. Lineage tracing analysis revealed that a subset of pdgfrb+ perivascular cells derive from tcf21 labeled epicardial cells. To see if disruption of Pdgfrb signaling impacts coronary development, I examined pdgfrb mutant hearts. In the Pdgfrb mutant, a mature coronary vessel network fails to form, and instead we observe isolated endothelial cell islands. Lastly, I characterized a transgenic line that expresses a dominant negative form of Pdgfrb (dnpdgfrb) and can be potentially used for later developmental and/or regenerative studies. My findings indicate strong dnpdgfrb induction can be achieved at adult stages. My studies will greatly enhance our current understanding of coronary vessel development, and can be used as the basis for studying perivascular cells and their interactions with endothelial cells after cardiac injury in regeneration.

歯科基礎医学会, 日下部 豊寿 = Toyohisa Kusakabe, 実験的歯の移動時における圧迫側歯槽骨に生じる背部骨吸収と血管分布 = Rear resorption at the pressure side incident in orthodontic tooth movement, 歯科基礎医学会雑誌, 39(6), DEC 1997, pp.623-640 / Hokkaido University (北海道大学) / 博士 / 歯学

Fluidized bed dryers (FBDs) are used in the pharmaceutical industry to remove excess moisture from granule prior to tablet formation. As granule moisture content is reduced from its initial to final state, the velocity required to fully fluidize the granule decreases and the bed voidage decreases. The change in these fluidization properties are attributed to the decrease in the interparticle force load created by a reduction in liquid bridging as moisture is removed. During constant velocity drying, these fluidization properties result in a bubbling fluidization state, which evolves into a bubble coalescing regime as drying proceeds. This behaviour was identifiable using pressure fluctuation time-series analysis techniques.<p> Distributor design studies using dry and wet granule in a conical fluidized bed suggest that the punched plate design limits bubble coalescence when compared to the perforated plate and Dutch weave mesh designs. Furthermore, the Dutch weave results in extensive segregation, which is undesirable from a fluidization perspective. Local drying hydrodynamic measurements using x-ray densitometry found that the punched and perforated plates generate a centralized bubbling core region during drying with a defluidized bed periphery. This fluidized core region grows as drying proceeds until the defluidized region disappears. Under the same operating conditions, a porous plate distributor creates extensive channelling and defluidization across the entire bed cross-section during the constant rate period of drying. These poor fluidization characteristics are a result of the porous plate introducing the gas into the bed as a fine dispersion.<p> Lastly, the hydrodynamics associated with the conical vessel geometry improves the circulation and mixing patterns in fluidized bed dryers. This is especially the case in the entry region of the conical bed where the high inlet gas velocity prevents defluidization around the periphery of the bed. The straight walled geometry of the cylindrical bed resulted in defluidization in this area. As a result, the hydrodynamics associated with bubbling differ significantly between the geometries over the course of drying.

Blood is a dense suspension of flexible red blood cells. In response to a background flow, these cells distribute themselves non-uniformly throughout the vessel. As a result, material properties that are well defined in homogeneous fluids, such as viscosity, are no longer so, and depend upon the flow geometry along with the particle properties. Using a simple model that accounts for the steady-state particle distribution in vessel flow, we derive an expression for the effective viscosity of blood and the suspension flow velocity field in a pressure-driven tube flow. <br /><br /> We derive the steady-state particle distribution from a conservation equation with convective flux arising from particle deformation in the flow. We then relate the particle microstructure to the overall flow through a generalized Newtonian stress-tensor, with the particle volume fraction appearing in the expression for the local viscosity. Comparing with experimental data, we show that the model quantitatively reproduces the observed rheology of blood in tube flow. <br /><br /> We reconsider the problem in an alternate geometry corresponding to the flow between two concentric cylinders. The steady-state particle distribution, suspension velocity field and the measured effective viscosity are all very different from their counterparts in tube flow, casting serious doubt upon the practice of using data from a Couette viscometer to parameterize constitutive models applied to vascular blood flow. <br /><br /> Finally, we calculate the effect of random fluctuations in the particle velocity on the averaged behaviour of the particle conservation equation. Using a smoothing method for linear stochastic differential equations, we derive a correction to the free Einstein-Stokes diffusion coeffcient that is due to the interaction of the particles with their neighbours.