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Search Results: 1 - 10 of 96918 matches for " Bruce W. Smith "
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Tuning Metamaterials for Applications at DUV Wavelengths
Andrew Estroff,Bruce W. Smith
International Journal of Optics , 2012, DOI: 10.1155/2012/603083
Abstract: The unique properties of metamaterials, namely, their negative refractive index, permittivity, or permeability, have gained much recent attention. Research into these materials has led to the realization of a host of applications that may be useful to enhance optical nanolithography. A selection of materials has been examined both experimentally and theoretically to verify their support of surface plasmons, or lack thereof, in the DUV spectrum via the attenuated total reflection (ATR) method using the Kretschmann configuration. At DUV wavelengths, materials that were previously useful at mid-UV and longer wavelengths no longer act as metamaterials. Structured materials comprised of alternating layers of aluminum and aluminum oxide (Al2O3), as well as some other absorption-free dielectrics, exhibit metamaterial behavior, as do some elemental materials such as aluminum. These elemental and structured materials exhibit the best properties for use in plasmonic nanolithographic applications. Therefore, a simulator was created to examine material and thickness combinations to generate a tunable metamaterial for use in the DUV. A method for performing plasmonic interference lithography with this metamaterial has been proposed, with calculations showing the potential for half-pitch imaging resolution of 25 nm.
Collaboration in Local Economic Development: The Case of Toledo
Neil Reid,Bruce W. Smith
Urbani Izziv , 2012,
Abstract: Many American communities place a high priority on retaining and attracting innovative industries. However, in most American metropolitan areas, the responsibility for local economic development is fragmented along jurisdictional and institutional lines. The result of this fragmentation is that local economic development is often chaotic with no one individual, agency, or jurisdiction in control, which may inhibit the effectiveness of local economic development efforts. To address these challenges and more effectively utilize resources, there has been greater emphasis recently on regional collaboration in local economic development. The purpose of this paper is to measure the extent of collaboration among local economic development professionals in the Toledo, Ohio Metropolitan Statistical Area and to identify the extent to which these interactions constitute a social network. We believe that the existence of a strong social network among economic development professionals is critical to overcome some of the negative effects of jurisdictional and institutional fragmentation. While there is a core network of relatively dense collaboration in northwest Ohio, that network does not span the entire metropolitan area. A high level of local interactions occurs, but there are few “global pipelines” outside the region. A potential challenge for economic development in the region is to avoid “lock in”, which will make it more difficult to attract innovative industries or diversify the economy in order to decrease the traditional dependence on the auto industry.
Bone Balance within a Cortical BMU: Local Controls of Bone Resorption and Formation
David W. Smith, Bruce S. Gardiner, Colin Dunstan
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0040268
Abstract: Maintaining bone volume during bone turnover by a BMU is known as bone balance. Balance is required to maintain structural integrity of the bone and is often dysregulated in disease. Consequently, understanding how a BMU controls bone balance is of considerable interest. This paper develops a methodology for identifying potential balance controls within a single cortical BMU. The theoretical framework developed offers the possibility of a directed search for biological processes compatible with the constraints of balance control. We first derive general control constraint equations and then introduce constitutive equations to identify potential control processes that link key variables that describe the state of the BMU. The paper describes specific local bone volume balance controls that may be associated with bone resorption and bone formation. Because bone resorption and formation both involve averaging over time, short-term fluctuations in the environment are removed, leaving the control systems to manage deviations in longer-term trends back towards their desired values. The length of time for averaging is much greater for bone formation than for bone resorption, which enables more filtering of variability in the bone formation environment. Remarkably, the duration for averaging of bone formation may also grow to control deviations in long-term trends of bone formation. Providing there is sufficient bone formation capacity by osteoblasts, this leads to an extraordinarily robust control mechanism that is independent of either osteoblast number or the cellular osteoid formation rate. A complex picture begins to emerge for the control of bone volume. Different control relationships may achieve the same objective, and the ‘integration of information’ occurring within a BMU may be interpreted as different sets of BMU control systems coming to the fore as different information is supplied to the BMU, which in turn leads to different observable BMU behaviors.
Maternal and infant vitamin D status during lactation: Is latitude important?  [PDF]
Carol L. Wagner, Cynthia R. Howard, Thomas C. Hulsey, Ruth A. Lawrence, Myla Ebeling, Judy Shary, Pamela G. Smith, Kristen Morella, Sarah N. Taylor, Bruce W. Hollis
Health (Health) , 2013, DOI: 10.4236/health.2013.512271
Abstract:

Background: The effect of latitude on maternal and infant vitamin D status during lactation is presumed to be strongly associated with higher rates of deficiency in those living at higher latitudes, yet with lifestyle changes, this conclusion may no longer be correct. Objective: To ascertain if higher latitude adversely affects the vitamin D status of lactating women and their fully breastfeeding infants. Study Design/Methods: Fully breastfeeding women and their infants were eligible for participation in this study as part of a larger prospective vitamin D supplementation trial. Women were recruited from two sites of differing latitude: Charleston, SC at 32°N and Rochester, NY at latitude 43°N. Maternal and infant baseline vitamin D status, intact parathyroid hormone (IPTH), serum calcium and phosphorus as a function of site/latitude were measured. The primary outcome was maternal and infant total circulating 25(OH)D at baseline by center/latitude, and the secondary outcome was the percent of women and infants who had achieved a baseline concentration of at least 20 ng/mL, meeting the Institute of Medicine’s definition of sufficiency at 4 to 6 weeks postpartum. Statistical analysis was performed using SAS version 9.3. Results: Higher latitude adversely affected vitamin D status only in lactating Caucasian women. African American and Hispanic women and infants living in Rochester compared to Charleston had improved vitamin D status, an effect that was no longer significant when controlling for socioeconomic factors and season. Overall, there was a significant vitamin D deficiency at baseline in lactating mothers, and a far greater deficiency in their infants. Maternal baseline 25(OH)D concentration remained positively associated with being Caucasian, BMI and summer months. Breastfeeding infant vitamin D status mirrored maternal status and remained positively associated with being Caucasian and summer months. Those infants who had been on a vitamin D supplement at the time of enrollment in the study had markedly

Cell Organisation in the Colonic Crypt: A Theoretical Comparison of the Pedigree and Niche Concepts
Richard C. van der Wath, Bruce S. Gardiner, Antony W. Burgess, David W. Smith
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0073204
Abstract: The intestinal mucosa is a monolayer of rapidly self-renewing epithelial cells which is not only responsible for absorption of water and nutrients into the bloodstream but also acts as a protective barrier against harmful microbes entering the body. New functional epithelial cells are produced from stem cells, and their proliferating progeny. These stem cells are found within millions of crypts (tubular pits) spaced along the intestinal tract. The entire intestinal epithelium is replaced every 2–3 days in mice (3–5 days in humans) and hence cell production, differentiation, migration and turnover need to be tightly regulated. Malfunctions in this regulation are strongly linked to inflammatory bowel diseases and to the formation of adenomas and ultimately cancerous tumours. Despite a great deal of biological experimentation and observation, precisely how colonic crypts are regulated to produce mature colonocytes remains unclear. To assist in understanding how cell organisation in crypts is achieved, two very different conceptual models of cell behaviour are developed here, referred to as the ‘pedigree’ and the ‘niche’ models. The pedigree model proposes that crypt cells are largely preprogrammed and receive minimal prompting from the environment as they move through a routine of cell differentiation and proliferation to become mature colonocytes. The niche model proposes that crypt cells are primarily influenced by the local microenvironments along the crypt, and that predetermined cell behaviour plays a negligible role in their development. In this paper we present a computational model of colonic crypts in the mouse, which enables a comparison of the quality and controllability of mature coloncyte production by crypts operating under these two contrasting conceptual models of crypt regulation.
Colon Cryptogenesis: Asymmetric Budding
Chin Wee Tan, Yumiko Hirokawa, Bruce S. Gardiner, David W. Smith, Antony W. Burgess
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0078519
Abstract: The process of crypt formation and the roles of Wnt and cell-cell adhesion signaling in cryptogenesis are not well described; but are important to the understanding of both normal and cancer colon crypt biology. A quantitative 3D-microscopy and image analysis technique is used to study the frequency, morphology and molecular topography associated with crypt formation. Measurements along the colon reveal the details of crypt formation and some key underlying biochemical signals regulating normal colon biology. Our measurements revealed an asymmetrical crypt budding process, contrary to the previously reported symmetrical fission of crypts. 3D immunofluorescence analyses reveals heterogeneity in the subcellular distribution of E-cadherin and β-catenin in distinct crypt populations. This heterogeneity was also found in asymmetrical budding crypts. Singular crypt formation (i.e. no multiple new crypts forming from one parent crypt) were observed in crypts isolated from the normal colon mucosa, suggestive of a singular constraint mechanism to prevent aberrant crypt production. The technique presented improves our understanding of cryptogenesis and suggests that excess colon crypt formation occurs when Wnt signaling is perturbed (e.g. by truncation of adenomatous polyposis coli, APC protein) in most colon cancers.
Computational Modeling of Fluid Flow and Intra-Ocular Pressure following Glaucoma Surgery
Bruce S. Gardiner,David W. Smith,Michael Coote,Jonathan G. Crowston
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0013178
Abstract: Glaucoma surgery is the most effective means for lowering intraocular pressure by providing a new route for fluid to exit the eye. This new pathway is through the sclera of the eye into sub-conjunctival tissue, where a fluid filled bleb typically forms under the conjunctiva. The long-term success of the procedure relies on the capacity of the sub-conjunctival tissue to absorb the excess fluid presented to it, without generating excessive scar tissue during tissue remodeling that will shut-down fluid flow. The role of inflammatory factors that promote scarring are well researched yet little is known regarding the impact of physical forces on the healing response.
A mathematical model for targeting chemicals to tissues by exploiting complex degradation
Bruce S Gardiner, Lihai Zhang, David W Smith, Peter Pivonka, Alan J Grodzinsky
Biology Direct , 2011, DOI: 10.1186/1745-6150-6-46
Abstract: For simplicity, we consider a one-dimensional geometry. In the special case where the rate of complex formation is small (compared to the diffusion timescale of the species within the tissue) the system can be solved analytically. This analytic solution allows us to show how the concentration of free chemical, a, in the tissue can be increased over the concentration of free chemical at the tissue boundary. We show that, under certain conditions, the maximum concentration of a can occur at the centre of the tissue, and give an upper bound on this maximum level. Numerical simulations are then used to determine how the behaviour of the system changes when the assumption of negligible complex formation rate is relaxed.We have shown, using our mathematical model, how complex degradation can potentially be exploited to target a chemical to a particular tissue, and how the level of the active chemical depends on factors such as the diffusion coefficients and degradation/production rates of each species. The biological significance of these results in terms of potential applications in cartilage tissue engineering and chemotherapy is discussed. In particular, we believe these results may be of use in determining the most promising prodrug candidates.A fundamental problem in biology and medicine is how to target a chemical to the particular tissue where it is to exert its biological action. Examples of chemicals to be targeted include endogenous hormones, growth factors and prescribed drugs. The advantage of targeting a drug to a particular tissue is that potential side-effects of the undesirable presence of the drug in other tissues are minimised.The results of a previous theoretical study describing the transport of IGF suggested a means of achieving selective targeting to particular tissues. Selective degradation of the IGF-IGFBP complex was shown to be capable of regulating the free concentration of IGF (the biologically active form) within a tissue. In some cases the fr
Modeling the Insulin-Like Growth Factor System in Articular Cartilage
Lihai Zhang, David W. Smith, Bruce S. Gardiner, Alan J. Grodzinsky
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0066870
Abstract: IGF signaling is involved in cell proliferation, differentiation and apoptosis in a wide range of tissues, both normal and diseased, and so IGF-IR has been the focus of intense interest as a promising drug target. In this computational study on cartilage, we focus on two questions: (i) what are the key factors influencing IGF-IR complex formation, and (ii) how might cells regulate IGF-IR complex formation? We develop a reaction-diffusion computational model of the IGF system involving twenty three parameters. A series of parametric and sensitivity studies are used to identify the key factors influencing IGF signaling. From the model we predict the free IGF and IGF-IR complex concentrations throughout the tissue. We estimate the degradation half-lives of free IGF-I and IGFBPs in normal cartilage to be 20 and 100 mins respectively, and conclude that regulation of the IGF half-life, either directly or indirectly via extracellular matrix IGF-BP protease concentrations, are two critical factors governing the IGF-IR complex formation in the cartilage. Further we find that cellular regulation of IGF-II production, the IGF-IIR concentration and its clearance rate, all significantly influence IGF signaling. It is likely that negative feedback processes via regulation of these factors tune IGF signaling within a tissue, which may help explain the recent failures of single target drug therapies aimed at modifying IGF signaling.
Modelling the anabolic response of bone using a cell population model
Pascal R. Buenzli,Peter Pivonka,Bruce S. Gardiner,David W. Smith
Physics , 2011, DOI: 10.1016/j.jtbi.2012.04.019
Abstract: To maintain bone mass during bone remodelling, coupling is required between bone resorption and bone formation. This coordination is achieved by a network of autocrine and paracrine signalling molecules between cells of the osteoclast lineage and cells of the osteoblastic lineage. Mathematical modelling of signalling between cells of both lineages can assist in the interpretation of experimental data, clarify signalling interactions and help develop a deeper understanding of complex bone diseases. In this paper, we further develop a mathematical model of bone cell interactions by Pivonka et al. (2008) to include the proliferation of precursor osteoblasts into the model. This inclusion is important to be able to account for Wnt signalling, believed to play an important role in anabolic responses of bone. We show that an increased rate of differentiation to precursor cells or an increased rate of proliferation of precursor osteoblasts themselves both result in increased bone mass. However, modelling these different processes separately enables the new model to represent recent experimental discoveries such as the role of Wnt signalling in bone biology and the recruitment of osteoblast progenitor cells by transforming growth factor \beta. Finally, we illustrate the power of the new model's capabilities by applying the model to prostate cancer metastasis to bone. In the bone microenvironment, prostate cancer cells are believed to release some of the same signalling molecules used to coordinate bone remodelling (i.e. Wnt and PTHrP), enabling the cancer cells to disrupt normal signalling and coordination between bone cells. This disruption can lead to either bone gain or bone loss. We demonstrate that the new computational model developed here is capable of capturing some key observations made on the evolution of the bone mass due to metastasis of prostate cancer to the bone microenvironment
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