99 research outputs found
A Sustainable Foundation
My intentions of this project are to investigate the potential of architecture to augment its efforts of sustainable strategies with aspirations of achieving a socially sustainable foundation in the urban setting. Within the context of Trenton, the understanding of the local communities, the capital and business districts, the education system, and the areas of renewal efforts can reveal solutions to the rebuilding of the city\u27s community by way of reconnecting these now divided forces. What makes architecture critical in this application is its ability to effectively address the very tangible aspects of sustainable practice and the potential for it to mold and facilitate the non-tangible efforts of social sustainability. The holistic, codependent approach necessary for sustainability to be a reality has every opportunity to synthesize and materialize in the form of truly beautiful architecture
A theoretical model of the application of RF energy to the airway wall and its experimental validation
<p>Abstract</p> <p>Background</p> <p>Bronchial thermoplasty is a novel technique designed to reduce an airway's ability to contract by reducing the amount of airway smooth muscle through controlled heating of the airway wall. This method has been examined in animal models and as a treatment for asthma in human subjects. At the present time, there has been little research published about how radiofrequency (RF) energy and heat is transferred to the airways of the lung during bronchial thermoplasty procedures. In this manuscript we describe a computational, theoretical model of the delivery of RF energy to the airway wall.</p> <p>Methods</p> <p>An electro-thermal finite-element-analysis model was designed to simulate the delivery of temperature controlled RF energy to airway walls of the in vivo lung. The model includes predictions of heat generation due to RF joule heating and transfer of heat within an airway wall due to thermal conduction. To implement the model, we use known physical characteristics and dimensions of the airway and lung tissues. The model predictions were tested with measurements of temperature, impedance, energy, and power in an experimental canine model.</p> <p>Results</p> <p>Model predictions of electrode temperature, voltage, and current, along with tissue impedance and delivered energy were compared to experiment measurements and were within ± 5% of experimental averages taken over 157 sample activations.</p> <p>The experimental results show remarkable agreement with the model predictions, and thus validate the use of this model to predict the heat generation and transfer within the airway wall following bronchial thermoplasty.</p> <p>Conclusions</p> <p>The model also demonstrated the importance of evaporation as a loss term that affected both electrical measurements and heat distribution. The model predictions showed excellent agreement with the empirical results, and thus support using the model to develop the next generation of devices for bronchial thermoplasty. Our results suggest that comparing model results to RF generator electrical measurements may be a useful tool in the early evaluation of a model.</p
High-speed 2D and 3D mid-IR imaging with an InGaAs camera
Recent work on mid-infrared (MIR) detection through the process of
non-degenerate two-photon absorption (NTA) in semiconducting materials has
shown that wide-field MIR imaging can be achieved with standard Si cameras.
While this approach enables MIR imaging at high pixel densities, the low
nonlinear absorption coefficient of Si prevents fast NTA-based imaging at lower
illumination doses. Here we overcome this limitation by using InGaAs as the
photosensor. Taking advantage of the much higher nonlinear absorption
coefficient of this direct bandgap semiconductor, we demonstrate high-speed MIR
imaging up to 500 fps with under 1 ms exposure per frame, enabling 2D or 3D
mapping without pre- or post-processing of the image.Comment: 7 pages, 5 Figure
Withaferin A Effectively Targets Soluble Vimentin in the Glaucoma Filtration Surgical Model of Fibrosis
Withaferin A (WFA) is a natural product that binds to soluble forms of the type III intermediate filament (IF) vimentin. Currently, it is unknown under what pathophysiological contexts vimentin is druggable, as cytoskeltal vimentin-IFs are abundantly expressed. To investigate druggability of vimentin, we exploited rabbit Tenon\u27s capsule fibroblast (RbTCF) cell cultures and the rabbit glaucoma filtration surgical (GFS) model of fibrosis. WFA potently caused G₀/G₁ cell cycle inhibition (IC₅₀ 25 nM) in RbTCFs, downregulating ubiquitin E3 ligase skp2 and inducing p27(Kip1) expression. Transforming growth factor (TGF)-ß-induced myofibroblast transformation caused development of cell spheroids with numerous elongated invadopodia, which WFA blocked potently by downregulating soluble vimentin and α-smooth muscle actin (SMA) expression. In the pilot proof-of-concept study using the GFS model, subconjunctival injections of a low WFA dose reduced skp2 expression in Tenon\u27s capsule and increased p27(Kip1) expression without significant alteration to vimentin-IFs. This treatment maintains significant nanomolar WFA concentrations in anterior segment tissues that correspond to WFA\u27s cell cycle targeting activity. A ten-fold higher WFA dose caused potent downregulation of soluble vimentin and skp2 expression, but as found in cell cultures, no further increase in p27(Kip1) expression was observed. Instead, this high WFA dose potently induced vimentin-IF disruption and downregulated α-SMA expression that mimicked WFA activity in TGF-ß-treated RbTCFs that blocked cell contractile activity at submicromolar concentrations. These findings illuminate that localized WFA injection to ocular tissues exerts pharmacological control over the skp2-p27(Kip1) pathway by targeting of soluble vimentin in a model of surgical fibrosis
The role of anion gap normalization time in the management of pediatric diabetic ketoacidosis
IntroductionOur aims were to determine whether anion gap normalization time (AGNT) correlates with risk factors related to the severity of diabetic ketoacidosis (DKA) in children, and to characterize AGNT as a criterion for DKA resolution in children admitted with moderate or severe disease.MethodsA ten-year retrospective cohort study of children admitted to the intensive care unit with DKA. We used a survival analysis approach to determine changes in serum glucose, bicarbonate, pH, and anion gap following admission. Using multivariate analysis, we examined associations between patients' demographic and laboratory characteristics with delayed normalization of the anion gap.ResultsA total of 95 patients were analyzed. The median AGNT was 8 h. Delayed AGNT (>8 h) correlated with pH < 7.1 and serum glucose >500 mg/dL. In multivariate analysis, glucose >500 mg/dL was associated with an increased risk for delayed AGNT, by 3.41 fold. Each 25 mg/dL elevation in glucose was associated with a 10% increment in risk for delayed AGNT. Median AGNT preceded median PICU discharge by 15 h (8 vs. 23 h).DiscussionAGNT represents a return to normal glucose-based physiology and an improvement in dehydration. The correlation observed between delayed AGNT and markers of DKA severity supports the usefulness of AGNT for assessing DKA recovery
The Role of Citrullination and the Type III Intermediate Filaments in Retinal Gliosis
Visual disorders are a massive economic and personal burden. Two leading causes of blindness in the United States, Glaucoma and Age-Related Macular Degeneration (AMD), currently have no cure. A major secondary issue in these diseases, often untreated, is the development and ongoing presence of scars in the eye. While scarring is a byproduct of the wound healing process, this scarring in the eye can lead to blindness. In the retina the scarring process is a result of ongoing retinal gliosis, mediated by the structural Müller glial cells. Two well-characterized markers of this process are the cytoskeletal Intermediate Filament (IF) proteins vimentin and the glial fibrillary acidic protein (GFAP), which become overexpressed as a stress response. Importantly, interfering with the soluble, non-cytoskeletal forms of these two proteins with the small molecule withaferin A (WFA) has anti-proliferative and anti-migratory effects, two cellular processes integral to scarring. As with many other proteins, GFAP and vimentin can be regulated by a number of different post-translational modifications (PTM). One PTM which the IF proteins are subjected to is citrullination.
Here, I have identified citrullination as an injury-induced response in the retina. Increases in citrullination are seen as early as 1 day after injury. This citrullination occurs along GFAP and vimentin filaments. I have identified two sites on GFAP that are citrullinated after retinal injury. The enzyme responsible for this injury-induced citrullination in the retina was PAD4. The citrullinated form of GFAP was targeted initially in a retinal explant system by the pan-PAD inhibitor Cl-amidine using an intravitreal injection model. The treatment decreased the levels of GFAP protein indicating a reduction of the gliotic phenotype. These findings mimicked what was seen in a mouse model of glaucoma, the DBA/2J mouse line. In this system, changes in citrullination within the glaucomatous eyes preceded changes in GFAP protein levels. These findings identify citrullination of GFAP as a major response to injury in the retina, mimicking the disease pathology of glaucoma. The ability to target these proteins within the retina, initially, and in the whole eye with an intravitreal injection to reduce a major gliotic marker has implications for the future development of therapeutics for treating the often undiagnosed gliosis associated with retinal disorders
Recalled to life The theology and spirituality of Mary Tudor's church
Available from British Library Document Supply Centre-DSC:DN052667 / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo
Clifford J. Rogers. War Cruel and Sharp: English Strategy under Edward III, 1327–1360. (Warfare in History.) Rochester, N.Y.: Boydell and Brewer. 2000. Pp. xviii, 458. $75.00. ISBN 0-85115-804-8.
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