895 research outputs found

    Ecological Risks from Agricultural Land Treated with Biosolids

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    Author Institution (Arvai and Basta): School of Environment and Natural Resources, The Ohio State University; Author Institution (Lanno): Department of Entomology, The Ohio State Universit

    Mechanisms of atrial flutter following epicardial high intensity focused ultrasound left atrial ablative procedures during concomitant cardiac surgery

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    AbstractIntroductionIatrogenic atrial tachyarrhythmias have increased with the widespread application of left atrial ablative procedures to treat atrial fibrillation.Methods and resultsEntrainment and activation mapping were utilized to study the mechanisms of atrial flutter in two patients who presented with atypical atrial flutter after high intensity focused ultrasound (HIFU) atrial ablation for persistent atrial fibrillation during the course of concomitant cardiac surgery. Case 1: Atrial flutter with CL of 340ms was demonstrated to be mediated by entry into and exit from the partially isolated posterior left atrium (LA) with conduction delay across at least one of the connections. The exit site was near the left superior pulmonary vein (LSPV) and the entrance site was near the right inferior pulmonary vein (RIPV) as demonstrated by activation and entrainment mapping. Case 2: Entrainment mapping was highly suggestive of inferior exit from the HIFU ablation line between the two inferior pulmonary veins. Flutter terminated during trans-septal procedure and could not be re-induced. Activation mapping of the LA during pacing revealed the inferior exit and left superior entrance site, both of which were successfully ablated, isolating the posterior LA.ConclusionsRe-entrant atrial flutter post-HIFU epicor Maze is caused by slow conduction at entry and exit sites from the otherwise isolated posterior LA wall. In both cases, gaps were found close to the LSPV and RIPV which may reflect difficulty in achieving proper contact between the HIFU device and the left atrial wall at these sites. These gaps are amenable to catheter ablation

    BIOCHEMICAL AND FUNCTIONAL CHARACTERIZATION OF A POTENTIAL 2’, 3’-CYCLIC-NUCLEOTIDE 3’-PHOSPHODIESTERASE (CNPASE) FOUND IN TUMORIGENIC FISH RETROVIRUSES

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    Tumorigenic retroviruses cause seasonal cancer in fish. Many of these retroviruses contain an interesting unknown gene of cellular origin. Computational programs predict that this gene encodes a CNPase (2’,3’-Cyclic-nucleotide 3’-phosphodiesterase). In mammals, the natural function of CNPase is unknown. The purpose of the experiment is to isolate and characterize the potential viral CNPase. Utilizing a vector from zebrafish endogenous retrovirus (ZFERV), the potential CNPase genetic sequence will be isolated and analyzed. Thereafter, the potential CNPase protein will be expressed and purified, and characterization will include enzymatic activity assays, inhibition activity studies, and NMR studies. Future studies involve functional characterization of the potential CNPase, including binding and transformation studies. Potential CNPase is predicted to function as an oncogene that promotes tumorigenesis in fish. Exploring this potential CNPase may aide in the treatment of affected fish as well as provide insight into the function of this enzyme in humans

    Laboratory implementation of edge illumination X-ray phase-contrast imaging with energy-resolved detectors

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    Edge illumination (EI) X-ray phase-contrast imaging (XPCI) has potential for applications in different fields of research, including materials science, non-destructive industrial testing, small-animal imaging, and medical imaging. One of its main advantages is the compatibility with laboratory equipment, in particular with conventional non-microfocal sources, which makes its exploitation in normal research laboratories possible. In this work, we demonstrate that the signal in laboratory implementations of EI can be correctly described with the use of the simplified geometrical optics. Besides enabling the derivation of simple expressions for the sensitivity and spatial resolution of a given EI setup, this model also highlights the EI’s achromaticity. With the aim of improving image quality, as well as to take advantage of the fact that all energies in the spectrum contribute to the image contrast, we carried out EI acquisitions using a photon-counting energy-resolved detector. The obtained results demonstrate that this approach has great potential for future laboratory implementations of EI. © (2015) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only

    PI3K Isoform-Specific Regulation of Leader and Follower Cell Function for Collective Migration and Proliferation in Response to Injury

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    To ensure proper wound healing it is important to elucidate the signaling cues that coordinate leader and follower cell behavior to promote collective migration and proliferation for wound healing in response to injury. Using an ex vivo post-cataract surgery wound healing model we investigated the role of class I phosphatidylinositol-3-kinase (PI3K) isoforms in this process. Our findings revealed a specific role for p110α signaling independent of Akt for promoting the collective migration and proliferation of the epithelium for wound closure. In addition, we found an important role for p110α signaling in orchestrating proper polarized cytoskeletal organization within both leader and wounded epithelial follower cells to coordinate their function for wound healing. p110α was necessary to signal the formation and persistence of vimentin rich-lamellipodia extensions by leader cells and the reorganization of actomyosin into stress fibers along the basal domains of the wounded lens epithelial follower cells for movement. Together, our study reveals a critical role for p110α in the collective migration of an epithelium in response to wounding

    Repression of nodal expression by maternal B1-type SOXs regulates germ layer formation in Xenopus and zebrafish

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    AbstractB1-type SOXs (SOXs 1, 2, and 3) are the most evolutionarily conserved subgroup of the SOX transcription factor family. To study their maternal functions, we used the affinity-purified antibody antiSOX3c, which inhibits the binding of Xenopus SOX3 to target DNA sequences [Development. 130(2003)5609]. The antibody also cross-reacts with zebrafish embryos. When injected into fertilized Xenopus or zebrafish eggs, antiSOX3c caused a profound gastrulation defect; this defect could be rescued by the injection of RNA encoding SOX3ΔC-EnR, a SOX3-engrailed repression domain chimera. In antiSOX3c-injected Xenopus embryos, normal animal–vegetal patterning of mesodermal and endodermal markers was disrupted, expression domains were shifted toward the animal pole, and the levels of the endodermal markers SOX17 and endodermin increased. In Xenopus, SOX3 acts as a negative regulator of Xnr5, which encodes a nodal-related TGFβ-family protein. Two nodal-related proteins are expressed in the early zebrafish embryo, squint and cyclops; antiSOX3c-injection leads to an increase in the level of cyclops expression. In both Xenopus and zebrafish, the antiSOX3c phenotype was rescued by the injection of RNA encoding the nodal inhibitor Cerberus-short (CerS). In Xenopus, antiSOX3c's effects on endodermin expression were suppressed by injection of RNA encoding a dominant negative version of Mixer or a morpholino against SOX17α2, both of which act downstream of nodal signaling in the endoderm specification pathway. Based on these data, it appears that maternal B1-type SOX functions together with the VegT/β-catenin system to regulate nodal expression and to establish the normal pattern of germ layer formation in Xenopus. A mechanistically conserved system appears to act in a similar manner in the zebrafish

    Xenotransplantation of microencapsulated pancreatic islets contained in a vascular prosthesis: preliminary results

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    Porcine and human pancreatic islets were microencapsulated in an alginate-polylysine biomembrane and put in a chamber of a new vascular prosthesis composed of an inner tubing of Dacron mesh and an outer tubing of expanded polytetrafluorethylene material. The vascular prosthesis was anastomized between the iliac artery and the contralateral vein of diabetic dogs. The recipients did not receive any immunosuppressive therapy. Function of porcine and human islets was monitored by measuring serum glucose levels and human C-peptide concentrations. After transplantation, serum glucose levels were maintained at values lower than 200 mg/dl, and C-peptide concentrations were between 0.8 and 3.2 ng/ml. Injected insulin requirements decreased by 50%-60%. Four to 8 weeks after transplantation, histologic examination showed well-preserved and functioning islets in the majority of intact microcapsules. Fibrin and inflammatory cells were not observed in the chamber. These data suggest long-term survival and function of microencapsulated pancreatic islets in the vascular prosthesis. © 1991 Springer-Verlag

    A REPEATED MEASURES ANALYSIS OF THE EFFECT OF VEGETATIVE BUFFERS ON CONTAMINANT RUNOFF FROM BERMUDAGRASS TURF

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    A repeated measures analysis was conducted on a set of data from a multi-year study to assess the effect of vegetative buffers on the surface runoff of selected herbicides and nutrients. Multiplicative models describing the observed behavior of runoff concentration over time for buffered and non-buffered plots were fitted on a log-transformed scale using linear mixed models with PROC MIXED in PC SAS version 6.11. A spatial power covariance structure was used. Additional models for contaminant mass flow rates were fitted to evaluate the effect of buffers on total runoff mass

    Bayesian Best-Arm Identification for Selecting Influenza Mitigation Strategies

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    Pandemic influenza has the epidemic potential to kill millions of people. While various preventive measures exist (i.a., vaccination and school closures), deciding on strategies that lead to their most effective and efficient use remains challenging. To this end, individual-based epidemiological models are essential to assist decision makers in determining the best strategy to curb epidemic spread. However, individual-based models are computationally intensive and it is therefore pivotal to identify the optimal strategy using a minimal amount of model evaluations. Additionally, as epidemiological modeling experiments need to be planned, a computational budget needs to be specified a priori. Consequently, we present a new sampling technique to optimize the evaluation of preventive strategies using fixed budget best-arm identification algorithms. We use epidemiological modeling theory to derive knowledge about the reward distribution which we exploit using Bayesian best-arm identification algorithms (i.e., Top-two Thompson sampling and BayesGap). We evaluate these algorithms in a realistic experimental setting and demonstrate that it is possible to identify the optimal strategy using only a limited number of model evaluations, i.e., 2-to-3 times faster compared to the uniform sampling method, the predominant technique used for epidemiological decision making in the literature. Finally, we contribute and evaluate a statistic for Top-two Thompson sampling to inform the decision makers about the confidence of an arm recommendation

    Fibrosis-the Tale of H3K27 Histone Methyltransferases and Demethylases

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    Fibrosis, or excessive scarring, is characterized by the emergence of alpha-smooth muscle actin (αSMA)-expressing myofibroblasts and the excessive accumulation of fibrotic extracellular matrix (ECM). Currently, there is a lack of effective treatment options for fibrosis, highlighting an unmet need to identify new therapeutic targets. The acquisition of a fibrotic phenotype is associated with changes in chromatin structure, a key determinant of gene transcription activation and repression. The major repressive histone mark, H3K27me3, has been linked to dynamic changes in gene expression in fibrosis through alterations in chromatin structure. H3K27-specific homologous histone methylase (HMT) enzymes, Enhancer of zeste 1 and 2 (EZH1, EZH2), which are the alternative subunits of the Polycomb Repressive Complex 2 (PRC2) and demethylase (KDM) enzymes, Ubiquitously transcribed tetratricopeptide repeat, X chromosome (UTX), and Lysine demethylase 6B (KDM6B), are responsible for regulating methylation status of H3K27me3. In this review, we explore how these key enzymes regulate chromatin structure to alter gene expression in fibrosis, highlighting them as attractive targets for the treatment of fibrosis
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