372 research outputs found

    Addressing Food Insecurity Within New American Communities in Vermont

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    Food insecurity is defined as not having safe, nutritious, or culturally appropriate foods available, or having limited ability to acquire these foods/uncertainty as to when one can acquire these foods. Reasons for food insecurity can be multifactorial such as language barriers, unfamiliar foods, and limited information about food environments.As a result, many turn to processed and energy- dense foods, contributing to the development of chronic diseases. Food banks and local food shelves provide supplemental food assistance to residents and communities in need. However, with diverse New American populations living within the same community, it is challenging to determine which foods best fit their needs. Vermont has welcomed 535 refugees in the last 4 years. Many of these new Americans currently reside in Winooski and Burlington. This study seeks to address the issues of mental health, food insecurity, access to the food shelf, and food preferences within the New American communities located in Winooski, Vermont.https://scholarworks.uvm.edu/comphp_gallery/1320/thumbnail.jp

    Silicon-organic hybrid (SOH) devices and their use in comb-based communication systems

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    Advanced wavelength-division multiplex-ing (WDM) requires both efficient multi-wavelength light sources to generate optical carriers and highly scalable photonic-electronic interfaces to encode data on these carriers. In this paper, we give an overview on our recent progress regarding silicon-organic hy-brid (SOH) integration and comb-based WDM transmission

    A potential new, stable state of the E-cadherin strand-swapped dimer in solution

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    E-cadherin is a transmembrane glycoprotein that facilitates inter-cellular adhesion in the epithelium. The ectodomain of the native structure is comprised of five repeated immunoglobulin-like domains. All E-cadherin crystal structures show the protein in one of three alternative conformations: a monomer, a strand-swapped trans homodimer and the so-called X-dimer, which is proposed to be a kinetic intermediate to forming the strand-swapped trans homodimer. However, previous studies have indicated that even once the trans strand-swapped dimer is formed, the complex is highly dynamic and the E-cadherin monomers may reorient relative to each other. Here, molecular dynamics simulations have been used to investigate the stability and conformational flexibility of the human E-cadherin trans strand-swapped dimer. In four independent, 100 ns simulations, the dimer moved away from the starting structure and converged to a previously unreported structure, which we call the Y-dimer. The Y-dimer was present for over 90% of the combined simulation time, suggesting that it represents a stable conformation of the E-cadherin dimer in solution. The Y-dimer conformation is stabilised by interactions present in both the trans strand-swapped dimer and X-dimer crystal structures, as well as additional interactions not found in any E-cadherin dimer crystal structures. The Y-dimer represents a previously unreported, stable conformation of the human E-cadherin trans strand-swapped dimer and suggests that the available crystal structures do not fully capture the conformations that the human E-cadherin trans homodimer adopts in solution

    Bridging ultrahigh-Q devices and photonic circuits

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    Optical microresonators are essential to a broad range of technologies and scientific disciplines. However, many of their applications rely on discrete devices to attain challenging combinations of ultra-low-loss performance (ultrahigh Q) and resonator design requirements. This prevents access to scalable fabrication methods for photonic integration and lithographic feature control. Indeed, finding a microfabrication bridge that connects ultrahigh-Q device functions with photonic circuits is a priority of the microcavity field. Here, an integrated resonator having a record Q factor over 200 million is presented. Its ultra-low-loss and flexible cavity design brings performance to integrated systems that has been the exclusive domain of discrete silica and crystalline microcavity devices. Two distinctly different devices are demonstrated: soliton sources with electronic repetition rates and high-coherence/low-threshold Brillouin lasers. This multi-device capability and performance from a single integrated cavity platform represents a critical advance for future photonic circuits and systems

    Long-term follow-up and treatment of congenital alveolar proteinosis

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    <p>Abstract</p> <p>Background</p> <p>Clinical presentation, diagnosis, management and outcome of molecularly defined congenital pulmonary alveolar proteinosis (PAP) due to mutations in the GM-CSF receptor are not well known.</p> <p>Case presentation</p> <p>A 2 1/2 years old girl was diagnosed as having alveolar proteinosis. Whole lung lavages were performed with a new catheter balloon technique, feasible in small sized airways. Because of some interstitial inflammation in the lung biopsy and to further improve the condition, empirical therapy with systemic steroids and azathioprin, and inhaled and subcutaneous GMCSF, were used. Based on clinical measures, total protein and lipid recovered by whole lung lavages, all these treatments were without benefit. Conversely, severe respiratory viral infections and an invasive aspergillosis with aspergilloma formation occurred. Recently the novel homozygous stop mutation p.Ser25X of the GMCSF receptor alpha chain was identified in the patient. This mutation leads to a lack of functional GMCSF receptor and a reduced response to GMCSF stimulation of CD11b expression of mononuclear cells of the patient. Subsequently a very intense treatment with monthly lavages was initiated, resulting for the first time in complete resolution of partial respiratory insufficiency and a significant improvement of the overall somato-psychosocial condition of the child.</p> <p>Conclusions</p> <p>The long term management from early childhood into young adolescence of severe alveolar proteinosis due to GMCSF receptor deficiency requires a dedicated specialized team to perform technically demanding whole lung lavages and cope with complications.</p

    Modeling Structure-Function Relationships in Synthetic DNA Sequences using Attribute Grammars

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    Recognizing that certain biological functions can be associated with specific DNA sequences has led various fields of biology to adopt the notion of the genetic part. This concept provides a finer level of granularity than the traditional notion of the gene. However, a method of formally relating how a set of parts relates to a function has not yet emerged. Synthetic biology both demands such a formalism and provides an ideal setting for testing hypotheses about relationships between DNA sequences and phenotypes beyond the gene-centric methods used in genetics. Attribute grammars are used in computer science to translate the text of a program source code into the computational operations it represents. By associating attributes with parts, modifying the value of these attributes using rules that describe the structure of DNA sequences, and using a multi-pass compilation process, it is possible to translate DNA sequences into molecular interaction network models. These capabilities are illustrated by simple example grammars expressing how gene expression rates are dependent upon single or multiple parts. The translation process is validated by systematically generating, translating, and simulating the phenotype of all the sequences in the design space generated by a small library of genetic parts. Attribute grammars represent a flexible framework connecting parts with models of biological function. They will be instrumental for building mathematical models of libraries of genetic constructs synthesized to characterize the function of genetic parts. This formalism is also expected to provide a solid foundation for the development of computer assisted design applications for synthetic biology

    Examination of polymorphic glutathione S-transferase (GST) genes, tobacco smoking and prostate cancer risk among Men of African Descent: A case-control study

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    <p>Abstract</p> <p>Background</p> <p>Polymorphisms in <it>glutathione S-transferase </it>(GST) genes may influence response to oxidative stress and modify prostate cancer (PCA) susceptibility. These enzymes generally detoxify endogenous and exogenous agents, but also participate in the activation and inactivation of oxidative metabolites that may contribute to PCA development. Genetic variations within selected <it>GST </it>genes may influence PCA risk following exposure to carcinogen compounds found in cigarette smoke and decreased the ability to detoxify them. Thus, we evaluated the effects of polymorphic <it>GSTs </it>(<it>M1</it>, <it>T1</it>, and <it>P1</it>) alone and combined with cigarette smoking on PCA susceptibility.</p> <p>Methods</p> <p>In order to evaluate the effects of <it>GST </it>polymorphisms in relation to PCA risk, we used TaqMan allelic discrimination assays along with a multi-faceted statistical strategy involving conventional and advanced statistical methodologies (e.g., Multifactor Dimensionality Reduction and Interaction Graphs). Genetic profiles collected from 873 men of African-descent (208 cases and 665 controls) were utilized to systematically evaluate the single and joint modifying effects of <it>GSTM1 </it>and <it>GSTT1 </it>gene deletions, <it>GSTP1 </it>105 Val and cigarette smoking on PCA risk.</p> <p>Results</p> <p>We observed a moderately significant association between risk among men possessing at least one variant <it>GSTP1 </it>105 Val allele (OR = 1.56; 95%CI = 0.95-2.58; p = 0.049), which was confirmed by MDR permutation testing (p = 0.001). We did not observe any significant single gene effects among <it>GSTM1 </it>(OR = 1.08; 95%CI = 0.65-1.82; p = 0.718) and <it>GSTT1 </it>(OR = 1.15; 95%CI = 0.66-2.02; p = 0.622) on PCA risk among all subjects. Although the <it>GSTM1</it>-<it>GSTP1 </it>pairwise combination was selected as the best two factor LR and MDR models (p = 0.01), assessment of the hierarchical entropy graph suggested that the observed synergistic effect was primarily driven by the <it>GSTP1 </it>Val marker. Notably, the <it>GSTM1</it>-<it>GSTP1 </it>axis did not provide additional information gain when compared to either loci alone based on a hierarchical entropy algorithm and graph. Smoking status did not significantly modify the relationship between the <it>GST </it>SNPs and PCA.</p> <p>Conclusion</p> <p>A moderately significant association was observed between PCA risk and men possessing at least one variant <it>GSTP1 </it>105 Val allele (p = 0.049) among men of African descent. We also observed a 2.1-fold increase in PCA risk associated with men possessing the <it>GSTP1 </it>(Val/Val) and <it>GSTM1 </it>(*1/*1 + *1/*0) alleles. MDR analysis validated these findings; detecting <it>GSTP1 </it>105 Val (p = 0.001) as the best single factor for predicting PCA risk. Our findings emphasize the importance of utilizing a combination of traditional and advanced statistical tools to identify and validate single gene and multi-locus interactions in relation to cancer susceptibility.</p

    Metabolically stable bradykinin B2 receptor agonists enhance transvascular drug delivery into malignant brain tumors by increasing drug half-life

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    <p>Abstract</p> <p>Background</p> <p>The intravenous co-infusion of labradimil, a metabolically stable bradykinin B2 receptor agonist, has been shown to temporarily enhance the transvascular delivery of small chemotherapy drugs, such as carboplatin, across the blood-brain tumor barrier. It has been thought that the primary mechanism by which labradimil does so is by acting selectively on tumor microvasculature to increase the local transvascular flow rate across the blood-brain tumor barrier. This mechanism of action does not explain why, in the clinical setting, carboplatin dosing based on patient renal function over-estimates the carboplatin dose required for target carboplatin exposure. In this study we investigated the systemic actions of labradimil, as well as other bradykinin B2 receptor agonists with a range of metabolic stabilities, in context of the local actions of the respective B2 receptor agonists on the blood-brain tumor barrier of rodent malignant gliomas.</p> <p>Methods</p> <p>Using dynamic contrast-enhanced MRI, the pharmacokinetics of gadolinium-diethyltriaminepentaacetic acid (Gd-DTPA), a small MRI contrast agent, were imaged in rodents bearing orthotopic RG-2 malignant gliomas. Baseline blood and brain tumor tissue pharmacokinetics were imaged with the 1<sup>st </sup>bolus of Gd-DTPA over the first hour, and then re-imaged with a 2<sup>nd </sup>bolus of Gd-DTPA over the second hour, during which normal saline or a bradykinin B2 receptor agonist was infused intravenously for 15 minutes. Changes in mean arterial blood pressure were recorded. Imaging data was analyzed using both qualitative and quantitative methods.</p> <p>Results</p> <p>The decrease in systemic blood pressure correlated with the known metabolic stability of the bradykinin B2 receptor agonist infused. Metabolically stable bradykinin B2 agonists, methionine-lysine-bradykinin and labradimil, had differential effects on the transvascular flow rate of Gd-DTPA across the blood-brain tumor barrier. Both methionine-lysine-bradykinin and labradimil increased the blood half-life of Gd-DTPA sufficiently enough to increase significantly the tumor tissue Gd-DTPA area under the time-concentration curve.</p> <p>Conclusion</p> <p>Metabolically stable bradykinin B2 receptor agonists, methionine-lysine-bradykinin and labradimil, enhance the transvascular delivery of small chemotherapy drugs across the BBTB of malignant gliomas by increasing the blood half-life of the co-infused drug. The selectivity of the increase in drug delivery into the malignant glioma tissue, but not into normal brain tissue or skeletal muscle tissue, is due to the inherent porous nature of the BBTB of malignant glioma microvasculature.</p
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